Month: June 2025

😳 A *Bit* Misleading

MaryO What do you think? , , , , , , , , , ,

Headline: “‘I gained 10st due to a rare condition – I lost it again by doing a simple daily exercise’
Hannah Mai, 37, managed to lose the weight in two years by doing a simple daily exercise”

She did lose the weight but, reading the article, also “Following her diagnosis, Hannah underwent brain surgery in February 2021 to remove the pituitary tumour causing her condition and was prescribed steroids to manage it.”

Just a bit of a misleading header.

Here’s the whole article.  And it was a bit more than a “simple daily exercise” and removing a pituitary tumor!

A woman who piled on 10 stone due to a rare condition has shed the weight in just two years, thanks to a daily exercise routine.

Hannah Mai, 37, was diagnosed with Cushing’s disease, a hormonal disorder caused by high cortisol levels, in October 2020 after gaining 10 stone in just two and a half years.

Following her diagnosis, Hannah underwent brain surgery in February 2021 to remove the pituitary tumour causing her condition and was prescribed steroids to manage it.

In April, 2023, Hannah was taken off her steroid medication and was determined to shed the 10 stone she gained due to the disease – who weighed 20 stone 5lbs and was a size 26.

Through a combination of high-protein meals and daily pilates sessions, Hannah impressively slimmed down to 10 stone 4lbs, fitting into a size 10, all within two years.

Hannah, from Coventry, Warwickshire, said: “Once I started losing the weight, I just kept going.

“It isn’t easy, you really have to push yourself, and focus on who you want to be and think about who you want to be.”

When she turned 30, Hannah noticed she started gaining weight and went from nine stone to 16 stone in a few months. She revealed that despite frequent doctor visits, she was constantly asked if she was expecting or if her weight gain was due to hormonal changes.

Hannah shared: “I was always around nine stone, but I noticed how I started to gain a bit of weight. I knew there was something wrong with me, but people around me thought I had changed my diet and asked if I was eating more.

“I was asked if I was pregnant six times, and told that my weight gain could be caused by hormones. I went up to 20 stone at my heaviest.”

In October 2020, over two years since her weight began to increase, Hannah woke up one day with a hunched back.

After a quick Google search suggested Cushing’s disease as a possible cause, and noticing the other symptoms including weight gain, she immediately sought medical advice.

She was referred to University Hospital Coventry & Warwickshire, where an MRI scan and blood tests confirmed she had Cushing’s disease.

Hannah added: “I printed off the list of symptoms and took them to my doctor, who then referred me to the hospital.

“There, I had an MRI scan and blood tests, which confirmed that I had Cushing’s disease.

“I was relieved but scared when I got the diagnosis. I had been saying for years that there was something wrong with me.”

Five months post-diagnosis, in February 2021, Hannah underwent brain surgery to remove the pituitary tumour causing the condition, and was put on steroids to manage her symptoms.

After battling with her health and spending two years on steroids to manage her condition, Hannah came off the medication as her health improved.

After she came off her medication, Hannah said she knew she was better and became determined to lose weight.

She said: “It wasn’t easy to lose weight whilst I was still on steroids, as soon as I came off them, I knew this was my body and I was a lot better.

“I really pushed myself, I worked super hard, cut out all sugar, cut out dairy, and gluten after I was diagnosed with celiac disease.

“I have a low-carb, high-protein diet with lots of vegetables, and I do pilates every day.”

Her commitment paid off as she impressively slimmed down from 20 stone to 10 stone within two years. She went from wearing a size 26 clothes to wearing a size 10 – back to where she was before Cushing’s disease.

Hannah said: “I am super proud of myself, I am always worried that the weight will come back.

“I feel so much happier. When I look back at myself, I just can’t believe I was that size.

“When I look back at old photos, I feel very sad about what happened to me, but it makes me think that I need to be proud about how far I have come.”

Adapted from https://www.mirror.co.uk/news/health/i-gained-10st-due-rare-35432462

ℹ️ Basics: The Pituitary Gland: Small But Mighty

MaryO Basic Info , , , , , , ,

 

The pituitary gland works hard to keep you healthy, doing everything from ensuring proper bone and muscle growth to helping nursing mothers produce milk for their babies. Its functionality is even more remarkable when you consider the gland is the size of a pea.

“The pituitary is commonly referred to as the ‘master’ gland because it does so many important jobs in the body,” says Karen Frankwich, MD, a board-certified endocrinologist at Mission Hospital. “Not only does the pituitary make its own hormones, but it also triggers hormone production in other glands. The pituitary is aided in its job by the hypothalamus. This part of the brain is situated above the pituitary, and sends messages to the gland on when to release or stimulate production of necessary hormones.”

These hormones include:

  • Growth hormone, for healthy bone and muscle mass
  • Thyroid-stimulating hormone, which signals the thyroid to produce its hormones that govern metabolism and the body’s nervous system, among others
  • Follicle-stimulating and luteinizing hormones for healthy reproductive systems (including ovarian egg development in women and sperm formation in men, as well as estrogen and testosterone production)
  • Prolactin, for breast milk production in nursing mothers
  • Adrenocorticotropin (ACTH), which prompts the adrenal glands to produce the stress hormone cortisol. The proper amount of cortisol helps the body adapt to stressful situations by affecting the immune and nervous systems, blood sugar levels, blood pressure and metabolism.
  • Antidiuretic (ADH), which helps the kidneys control urine levels
  • Oxytocin, which can stimulate labor in pregnant women

The work of the pituitary gland can be affected by non-cancerous tumors called adenomas. “These tumors can affect hormone production, so you have too little or too much of a certain hormone,” Dr. Frankwich says. “Larger tumors that are more than 1 centimeter, called macroadenomas, can also put pressure on the area surrounding the gland, which can lead to vision problems and headaches. Because symptoms can vary depending on the hormone that is affected by a tumor, or sometimes there are no symptoms, adenomas can be difficult to pinpoint. General symptoms can include nausea, weight loss or gain, sluggishness or weakness, and changes in menstruation for women and sex drive for men.”

If there’s a suspected tumor, a doctor will usually run tests on a patient’s blood and urine, and possibly order a brain-imaging scan. An endocrinologist can help guide a patient on the best course of treatment, which could consist of surgery, medication, radiation therapy or careful monitoring of the tumor if it hasn’t caused major disruption.

“The pituitary gland is integral to a healthy, well-functioning body in so many ways,” Dr. Frankwich says. “It may not be a major organ you think about much, but it’s important to know how it works, and how it touches on so many aspects of your health.”

Adapted from http://www.stjhs.org/HealthCalling/2016/December/The-Pituitary-Gland-Small-but-Mighty.aspx

Thoughts? Share on the message boards.

ℹ️ Basics: Testing: IGF-1 (Insulin-like growth factor 1)

MaryO Basic Info , , , , , ,

Aim—To contribute to the debate about whether growth hormone (GH) and insulin-like growth factor 1 (IGF-1) act independently on the growth process.

Methods—To describe growth in human and animal models of isolated IGF-1 deficiency (IGHD), such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and IGF-1 gene or GH receptor gene knockout (KO) mice.

Results—Since the description of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS are shorter (42–47 cm) than healthy babies (49–52 cm), suggesting that IGF-1 has some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30% smaller. The postnatal growth rate of patients with LS is very slow, the distance from the lowest normal centile increasing progressively. If untreated, the final height is 100–136 cm for female and 109–138 cm for male patients. They have acromicia, organomicria including the brain, heart, gonads, genitalia, and retardation of skeletal maturation. The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS. It accelerated linear growth rates to 8–9 cm in the first year of treatment, compared with 10–12 cm/year during GH treatment of IGHD. The growth rate in following years was 5–6.5 cm/year.

Conclusion—IGF-1 is an important growth hormone, mediating the protein anabolic and linear growth promoting effect of pituitary GH. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH.

Keywords: insulin-like growth factor I, growth hormones, Laron syndrome, growth

In recent years, new technologies have enabled many advances in the so called growth hormone (GH) axis (fig 1▶). Thus, it has been found that GH secretion from the anterior pituitary is regulated not only by GH releasing hormone (GHRH) and somatostatin (GH secretion inhibiting hormone), but also by other hypothalamic peptides called GH secretagogues, which seem to act in synergism with GHRH by inhibiting somatostatin. One of these has been cloned and named Ghrelin. The interplay between GHRH and somatostatin induces a pulsatile GH secretion, which is highest during puberty. GH induces the generation of insulin-like growth factor 1 (IGF-1, also called somatomedin 1) in the liver and regulates the paracrine production of IGF-1 in many other tissues.

IGF-1

IGF-1 and IGF-2 were identified in 1957 by Salmon and Daughaday and designated “sulphation factor” by their ability to stimulate 35-sulphate incorporation into rat cartilage. Froesch et al described the non-suppressible insulin-like activity (NSILA) of two soluble serum components (NSILA I and II). In 1972, the labels sulphation factor and NSILA were replaced by the term “somatomedin”, denoting a substance under control and mediating the effects of GH. In 1976, Rinderknecht and Humbel isolated two active substances from human serum, which owing to their structural resemblance to proinsulin were renamed “insulin-like growth factor 1 and 2” (IGF-1 and 2). IGF-1 is the mediator of the anabolic and mitogenic activity of GH.

CHEMICAL STRUCTURE

The IGFs are members of a family of insulin related peptides that include relaxin and several peptides isolated from lower invertebrates. IGF-1 is a small peptide consisting of 70 amino acids with a molecular weight of 7649 Da. Similar to insulin, IGF-1 has an A and B chain connected by disulphide bonds. The C peptide region has 12 amino acids. The structural similarity to insulin explains the ability of IGF-1 to bind (with low affinity) to the insulin receptor.

THE IGF-1 GENE

The IGF-1 gene is on the long arm of chromosome 12q23–23. The human IGF-1 gene consists of six exons, including two leader exons, and has two promoters.

IGF binding proteins (IGFBPs)

In the plasma, 99% of IGFs are complexed to a family of binding proteins, which modulate the availability of free IGF-1 to the tissues. There are six binding proteins. In humans, almost 80% of circulating IGF-1 is carried by IGFBP-3, a ternary complex consisting of one molecule of IGF-1, one molecule of IGFBP-3, and one molecule of an 88 kDa protein named acid labile subunit. IGFBP-1 is regulated by insulin and IGF-1; IGFBP-3 is regulated mainly by GH but also to some degree by IGF-1.

The IGF-1 receptor

The human IGF-1 receptor (type 1 receptor) is the product of a single copy gene spanning over 100 kb of genomic DNA at the end of the long arm of chromosome 15q25–26. The gene contains 21 exons (fig 2▶) and its organisation resembles that of the structurally related insulin receptor (fig 3▶). The type 1 IGF receptor gene is expressed by almost all tissues and cell types during embryogenesis. In the liver, the organ with the highest IGF-1 ligand expression, IGF-1 receptor mRNA is almost undetectable, possibly because of the “downregulation” of the receptor by the local production of IGF-1. The type 1 IGF receptor is a heterotetramer composed of two extracellular spanning α subunits and transmembrane β subunits. The α subunits have binding sites for IGF-1 and are linked by disulphide bonds (fig 3▶). The β subunit has a short extracellular domain, a transmembrane domain, and an intracellular domain. The intracellular part contains a tyrosine kinase domain, which constitutes the signal transduction mechanism. Similar to the insulin receptor, the IGF-1 receptor undergoes ligand induced autophosphorylation. The activated IGF-1 receptor is capable of phosphorylating other tyrosine containing substrates, such as insulin receptor substrate 1 (IRS-1), and continues a cascade of enzyme activations via phosphatidylinositol-3 kinase (PI3-kinase), Grb2 (growth factor receptor bound protein 2), Syp (a phophotyrosine phosphatase), Nck (an oncogenic protein), and Shc (src homology domain protein), which associated to Grb2, activates Raf, leading to a cascade of protein kinases including Raf, mitogen activated protein (MAP) kinase, 5 G kinase, and others.

Physiology

IGF-1 is secreted by many tissues and the secretory site seems to determine its actions. Most IGF-1 is secreted by the liver and is transported to other tissues, acting as an endocrine hormone. IGF-1 is also secreted by other tissues, including cartilagenous cells, and acts locally as a paracrine hormone (fig 4▶). It is also assumed that IGF-1 can act in an autocrine manner as an oncogene. The role of IGF-1 in the metabolism of many tissues including growth has been reviewed recently.

Is IGF-1 “a” or “the” growth hormone?

The discussion on the role of IGF-1 in body growth will be based on growth in states of IGF-1 deficiency and the effects of exogenous IGF-1 administration. Experiments in nature (gene deletion or gene mutations) or experimental models in animals, such as gene knockouts, help us in this endeavour. In 1966 and 1968, we described a new type of dwarfism indistinguishable from genetic isolated GH deficiency (IGHD), but characterised by high serum GH values. Subsequent studies revealed that these patients cannot generate IGF-1.

This syndrome of GH resistance (insensitivity) was named by Elders et al as Laron dwarfism, a name subsequently changed to Laron syndrome (LS). Molecular studies revealed that the causes of GH resistance are deletions or mutations in the GH receptor gene, resulting in the failure to generate IGF-1 and a reduction in the synthesis of several other substances, including IGFBP-3. This unique model in humans has enabled the study of the differential effects of GH and IGF-1.

Growth and development in congenital (primary) IGF-1 deficiency (LS)

Our group has studied and followed 52 patients (many since birth) throughout childhood, puberty, and into adulthood. We found that newborns with LS are slightly shorter at birth (42–47 cm) than healthy babies (49–52 cm), suggesting that IGF-1 has some influence on intrauterine linear growth. This fact is enforced by the findings that already at birth, and throughout childhood, skeletal maturation is retarded, as is organ growth. These growth abnormalities include a small brain (as expressed by head circumference), a small heart (cardiomicria), and acromicria (small chin, resulting from underdevelopment of the facial bones, small hands, and small feet). IGF-1 deficiency also causes underdevelopment and weakness of the muscular system, and impairs and weakens hair and nail growth. These findings are identical to those described in IGHD. IGF-1 deficiency throughout childhood causes dwarfism (final height if untreated, 100–135 cm in female and 110–142 cm in male patients), with an abnormally high upper to lower body ratio. One patient reported from the UK was found to have a deletion of exons 4 and 5 of the IGF-1 gene and he too was found to have severe growth retardation.

Impaired growth and skeletal development in the absence of IGF-1 were confirmed in mice using knockout (KO) of the IGF-1 gene or GH receptor gene.

Knockout of the IGF-1 gene or the IGF-1 receptor gene reduces the size of mice by 40–45%. Lack of the IGF-1 receptor is lethal at birth in mice owing to respiratory failure caused by impaired development of the diaphragm and intercostal muscles. In another model, the mice remained alive and their postnatal growth was reduced.

In conclusion, findings in humans and in animals show that IGF-1 deficiencies causes pronounced growth retardation in the presence of increased GH values.

The following is a summary of the results of the growth stimulating effects of the administration of exogenous IGF-1 to children and experimental data.

Growth promoting effects of IGF-1

The first demonstration that exogenous IGF-1 stimulates growth was the administration of purified hormone to hypophysectomised rats. After the biosynthesis of IGF-1 identical to the native hormone, trials of its use in humans were begun; first in adults and then in children. Our group was the first to introduce long term administration of biosynthetic IGF-1 to children with primary IGF-1 deficiency—primary GH insensitivity or LS. The finding that daily IGF-1 administration raises serum alkaline phosphatose, which is an indicator of osteoblastic activity, and serum procollagen, in addition to IGFBP-3, led to long term treatment. Treatment of patients with LS was also initiated in other parts of the world. The difference between us and the other groups was that we used a once daily dose, whereas the others administered IGF-1 twice daily. Table 1▶ compares the linear growth response of children with LS treated by four different groups. It can be seen that before treatment the mean growth velocity was 3–4.7 cm/year and that this increased after IGF-1 treatment to 8.2–9.1 cm/year, followed by a lower velocity of 5.5–6.4 cm/year in the next two years. (In GH treatment the highest growth velocity registered is also in the first year of treatment.) Figure 5▶ illustrates the growth response to IGF-1 in eight children during the first years of treatment. Ranke and colleagues reported that two of their patients had reached the third centile (Tanner), as did the patient of Krzisnik and Battelino; however, most patients did not reach a normal final height. The reasons may be late initiation of treatment, irregular IGF-1 administration, underdosage, etc. Ranke et al conclude that long term treatment of patients with LS promoted growth and, if treatment is started at an early age, there is a considerable potential for achieving height normalisation. Because no patient in our group was treated since early infancy to final height we cannot confirm this opinion.

Table 1

Linear growth response of children with Laron syndrome treated by means of insulin-like growth factor 1 (IGF-1)

At start Growth velocity (cm/year) Year of treatment
Authors Year Ref. N Age range (years) BA (years) Ht SDS (m) IGF-1 dose (μg/kg/day) 0 1st 2nd 3rd
(n = 26) (n = 18)
Ranke et al 1995 31 3.7–19 1.8–13.3 −6.5 40–120 b.i.d. 3.9 (1.8) 8.5 (2.1) 6.4 (2.2)
(n = 5) (n = 5) (n = 1)
Backeljauw et al 1996 5 2–11 0.3–6.8 −5.6 80–120 b.i.d. 4.0 9.3 6.2 6.2
(n = 9) (n = 6) (n = 5)
Klinger and Laron 1995 9 0.5–14 0.2–11 −5.6 150–200 i.d 4.7 (1.3) 8.2 (0.8) 6 (1.3) 4.8 (1.3)*
(n = 15) (n = 15) (n = 6)
Guevarra-Aguirre et al 1997 15 3.1–17 4.5–9.3 120 b.i.d. 3.4 (1.4) 8.8 (11) 6.4 (1.1) 5.7 (1.4)
(n = 8) (n = 8)
Guevarra-Aguire et al 8 80 b.i.d. 3.0 (1.8) 9.1 (2.2) 5.6 (2.1)

Growth velocity values are mean (SD).

*The younger children had a growth velocity of 5.5 and 6.5 cm/year.

BA, bone age; b.i.d., twice daily; CA, chronological age; i.d., once daily; Ht SDS, height standard deviation score.

When the growth response to GH treatment in infants with IGHD was compared with that of IGF-1 in infants with LS we found that the infants with IGHD responded faster and better than those with LS. However, the small number of patients and the differences in growth retardation between the two groups makes it difficult to reach a conclusion.

Both hormones stimulated linear growth, but GH seemed more effective than IGF-1. One cause may be the greater growth deficit of the infants with LS than those with IGHD, an insufficient dose of IGF-1, or that there is a need for some GH to provide an adequate stem cell population of prechondrocytes to enable full expression of the growth promoting action of IGF-1, as postulated by Green and colleagues and Ohlson et al. All the above findings based on a few clinical studies with small groups of patients and a few experimental studies remain at present controversial. The crucial question is whether there are any, and if so, whether there are sufficient IGF-1 receptors in the “progenitor cartilage zone” of the epiphyseal cartilage (fig 4▶) to respond to endocrine and exogenous IGF-1. Using the mandibular condyle of 2 day old ICR mice, Maor et al showed that these condyles, which resemble the epiphyseal plates of the long bones, contain IGF-1 and high affinity IGF-1 receptors also in the chondroprogenitor cell layers, which enables them to respond to IGF-1 in vitro.

Sims et al, using mice with GH receptor KO showed that IGF-1 administration stimulates the growth (width) of the tibial growth plate and that IGF-1 has a GH independent effect on the growth plate. These findings are similar to those found when treating hypophysectomised rats with IGF-1.

In conclusion, IGF-1 is an important growth hormone, mediating the anabolic and linear growth promoting effect of pituitary GH protein. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH.

References

1. Tannenbaum GS, Ling N. The interrelationship of growth hormone (GH)-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion. Endocrinology 1984;115:1952–7. [PubMed] []
2. Laron Z. Growth hormone secretagogues: clinical experience and therapeutic potential. Drugs 1995;50:595–601. [PubMed] []
3. Ghigo E, Boghen M, Casanueva FF, et al., eds. Growth hormone secretagogues. Basic findings and clinical implications. Amsterdam: Elsevier, 1994.
4. Jaffe CA, Ho PJ, Demott-Friberg R, et al. Effects of a prolonged growth hormone (GH)-releasing peptide infusion on pulsatile GH secretion in normal men. J Clin Endocrinol Metab 1993;77:1641–7. [PubMed] []
5. Kojima M, Hosada H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656–60. [PubMed] []
6. Devesa J, Lima L, Tresquerres AF. Neuroendocrine control of growth hormone secretion in humans. Trends Endocrinol Metab 1992;3:175–83. [PubMed] []
7. Laron Z. The somatostatin-GHRH-GH-IGF-I axis. In: Merimee T, Laron Z, eds. Growth hormone, IGF-I and growth: new views of old concepts. Modern endocrinology and diabetes, Vol. 4. London-Tel Aviv: Freund Publishing House Ltd, 1996:5–10.
8. Salmon WD, Jr, Daughaday W. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med 1957;49:825–36. [PubMed] []
9. Froesch ER, Burgi H, Ramseier EB, et al. Antibody-suppressible and nonsuppressible insulin-like activities in human serum and their physiologic significance. An insulin assay with adipose tissue of increased precision and specificity. J Clin Invest 1963;42:1816–34. [PMC free article] [PubMed] []
10. Daughaday WH, Hall K, Raben MS, et al. Somatomedin: a proposed designation for the sulfation factor. Nature 1972;235:107. [PubMed] []
11. Rinderknecht E, Humbel RE. Polypeptides with non-suppressible insulin-like and cell-growth promoting activities in human serum: isolation, chemical characterization, and some biological properties of forms I and II. Proc Natl Acad Sci U S A 1976;73:2365–9. [PMC free article] [PubMed] []
12. Laron Z. Somatomedin-1 (recombinant insulin-like growth factor-I). Clinical pharmacology and potential treatment of endocrine and metabolic disorders. Biodrugs 1999;11:55–70. [PubMed] []
13. Blundell TL, Humbel RE. Hormone families: pancreatic hormones and homologous growth factors. Nature 1980;287:781–7. [PubMed] []
14. Rinderknecht E, Humbel RE. The amino acid sequence of human insulin like growth factor I and its structural homology, with proinsulin. J Biol Chem 1978;253:2769–76. [PubMed] []
15. Brissenden JE, Ullrich A, Francke U. Human chromosomal mapping of genes for insulin-like growth factors I and II and epidermal growth factor. Nature 1984;310:781–4. [PubMed] []
16. Mullis PE, Patel MS, Brickell PM, et al. Growth characteristics and response to growth hormone therapy in patients with hypochondroplasia: genetic linkage of the insulin-like growth factor I gene at chromosome 12q23 to the disease in a subgroup of these patients. Clin Endocrinol 1991;34:265–74. [PubMed] []
17. Rotwein P. Structure, evolution, expression and regulation of insulin-like growth factors I and II. Growth Factors 1991;5:3–18. [PubMed] []
18. Hwa V, Oh Y, Rosenfeld RG. The insulin-like growth factor binding protein (IGFBP) superfamily. Endocr Rev 1999;20:761–87 [PubMed] []
19. Lewitt MS, Saunders H, Phuyal JL, et al. Complex formation by human insulin-like growth factor-binding protein-3 and human acid-labile subunit in growth hormone-deficient rats. Endocrinology 1994;134:2402–9. [PubMed] []
20. Laron Z, Suikkairi AM, Klinger B, et al. Growth hormone and insulin-like growth factor regulate insulin-like growth factor-binding protein-1 in Laron type dwarfism, growth hormone deficiency and constitutional short stature. Acta Endocrinol 1992;127:351–8. [PubMed] []
21. Kanety H, Karasik A, Klinger B, et al. Long-term treatment of Laron type dwarfs with insulin-like growth factor I increases serum insulin-like growth factor-binding protein 3 in the absence of growth hormone activity. Acta Endocrinol 1993;128:144–9. [PubMed] []
22. Werner H. Molecular biology of the type I IGF receptor. In: Rosenfeld RG, Roberts CT, Jr, eds. The IGF system—molecular biology, physiology and clinical applications. Totowa, NJ: Humana Press, 1999:63–88.
23. Seino S, Seino M, Nishi S, et al. Structure of the human insulin receptor gene and characterization of its promoter. Proc Natl Acad Sci U S A 1989;86:114–18. [PMC free article] [PubMed] []
24. Bondy CA, Werner H, Roberts CT, Jr, et al. Cellular pattern of insulin-like growth factor I (IGF-I) and type I IGF receptor gene expression in early organogenesis: comparison with IGF-II gene expression. Mol Endocrinol 1990;4:1386–98. [PubMed] []
25. Kato H, Faria TN, Stannard B, et al. Essential role of tyrosine residues 1131, 1135, and 1136 of the insulin-like growth factor-I (IGF-I) receptor in IGF-I action. Mol Endocrinol 1994;8:40–50. [PubMed] []
26. LeRoith D, Werner H, Beitner-Johnson D, et al. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 1995;16:143–63. [PubMed] []
27. Merimee T, Laron Z, eds. Growth hormone, IGF-I and growth: new views of old concepts. Modern endocrinology and diabetes, Vol. 4. London-Tel Aviv: Freund Publishing House Ltd, 1996.
28. D’Ercole AJ, Applewhite GT, Underwood LE. Evidence that somatomedin is synthesized by multiple tissues in the fetus. Dev Biol 1980;75:315–28 [PubMed] []
29. Nilsson A, Isgaard J, Lindhahl A, et al. Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate. Science 1986;233:571–4. [PubMed] []
30. Baserga R. The IGF-I receptor in cancer research. Exp Cell Res 1999;253:1–6. [PubMed] []
31. Rosenfeld RG, Roberts CT, Jr, eds. The IGF system—molecular biology, physiology and clinical applications. Totowa, NY: Humana Press, 1999.
32. Zapf J, Froesch ER. Insulin-like growth factor I actions on somatic growth. In: Kostyo J, ed. Handbook of physiology, Vol. V, Section 7. Philadelphia: American Physiological Society, 1999:663–99.
33. Laron Z, Pertzelan A, Mannheimer S. Genetic pituitary dwarfism with high serum concentration of growth hormone. A new inborn error of metabolism? Isr J Med Sci 1966;2:153–5. [PubMed] []
34. Laron Z, Pertzelan A, Karp M. Pituitary dwarfism with high serum levels of growth hormone. Isr J Med Sci 1968;4:883–94. [PubMed] []
35. Laron Z, Pertzelan A, Karp M, et al. Administration of growth hormone to patients with familial dwarfism with high plasma immunoreactive growth hormone. Measurement of sulfation factor, metabolic and linear growth responses. J Clin Endocrinol Metab 1971;33:332–42. [PubMed] []
36. Elders MJ, Garland JT, Daughaday WH, et al. Laron’s dwarfism: studies on the nature of the defect. J Pediatr 1973;83:253–63. [PubMed] []
37. Laron Z, Parks JS, eds. Lessons from Laron syndrome (LS) 1966–1992. A model of GH and IGF-I action and interaction. Pediatric and Adolescent Endocrinology 1993;24:1–367. []
38. Godowski PJ, Leung DW, Meacham LR, et al. Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in 2 patients with Laron type dwarfism. Proc Natl Acad Sci U S A 1989;86:8083–7. [PMC free article] [PubMed] []
39. Amselem S, Duquesnoy P, Attree O, et al. Laron dwarfism and mutations of the growth hormone-receptor gene. N Engl J Med 1989;321:989–95. [PubMed] []
40. Laron Z. Laron syndrome—primary growth hormone resistance. In: Jameson JL, ed. Hormone resistance syndromes. Contemporary endocrinology, Vol. 2. Totowa, NJ: Humana Press, 1999:17–37.
41. Laron Z. Laron type dwarfism (hereditary somatomedin deficiency): a review. In: Frick P, Von Harnack GA, Kochsiek GA, et al, eds. Advances in internal medicine and pediatrics. Berlin-Heidelberg: Springer-Verlag, 1984:117–50. [PubMed]
42. Feinberg MS, Scheinowitz M, Laron Z. Echocardiographic dimensions and function in adults with primary growth hormone resistance (Laron syndrome). Am J Cardiol 2000;85:209–13. [PubMed] []
43. Brat O, Ziv I, Klinger B, et al. Muscle force and endurance in untreated and human growth hormone or insulin-like growth factor-I-treated patients with growth hormone deficiency or Laron syndrome. Horm Res 1997;47:45–8. [PubMed] []
44. Lurie R, Ben-Amitai D, Laron Z. Impaired hair growth and structural defects in patients with Laron syndrome (primary IGF-I deficiency) [abstract]. Horm Res 2001 [In press.]
45. Gluckman PD, Gunn AJ, Wray A, et al. Congenital idiopathic growth hormone deficiency associated with prenatal and early postnatal growth failure. J Pediatr 1992;121:920–3. [PubMed] []
46. Woods KA, Camacho-Hubner C, Savage MO, et al. Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med 1996;335:1363–7. [PubMed] []
47. Zhou Y, Xu BC, Maheshwari HG, et al. A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). Proc Natl Acad Sci U S A 1997;94:13215–20. [PMC free article] [PubMed] []
48. Sjogren K, Bohlooly YM, Olsson B, et al. Disproportional skeletal growth and markedly decreased bone mineral content in growth hormone receptor –/– mice. Biochem Biophys Res Commun 2000;267:603–8. [PubMed] []
49. Accili D, Nakae J, Kim JJ, et al. Targeted gene mutations define the roles of insulin and IGF-I receptors in mouse embryonic development. J Pediatr Endocrinol Metab 1999;12:475–85. [PubMed] []
50. Holzenberger M, Leneuve P, Hamard G, et al. A targeted partial invalidation of the insulin-like growth factor-I receptor gene in mice causes a postnatal growth deficit. Endocrinology 2000;141:2557–66. [PubMed] []
51. Schoenle E, Zapf J, Humbel RE, et al. Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature 1982;296:252–3. [PubMed] []
52. Guler H-P, Zapf J, Scheiwiller E, et al. Recombinant human insulin-like growth factor I stimulates growth and has distinct effects on organ size in hypophysectomized rats. Proc Natl Acad Sci U S A 1988;85:4889–93. [PMC free article] [PubMed] []
53. Niwa M, Sato Y, Saito Y, et al. Chemical synthesis, cloning and expression of genes for human somatomedin C (insulin like growth factor I) and 59Val somatomedin C. Ann N Y Acad Sci 1986;469:31–52. [PubMed] []
54. Guler HP, Zapf J, Froesch ER. Short term metabolic effects of recombinant human insulin like growth factor in healthy adults. N Engl J Med 1987;317:137–40. [PubMed] []
55. Laron Z, Klinger B, Silbergeld A, et al. Intravenous administration of recombinant IGF-I lowers serum GHRH and TSH. Acta Endocrinol 1990;123:378–82. [PubMed] []
56. Klinger B, Garty M, Silbergeld A, et al. Elimination characteristics of intravenously administered rIGF-I in Laron type dwarfs (LTD). Dev Pharmacol Ther 1990;15:196–9. [PubMed] []
57. Laron Z, Klinger B, Jensen LT, et al. Biochemical and hormonal changes induced by one week of administration of rIGF-I to patients with Laron type dwarfism. Clin Endocrinol 1991;35:145–50. [PubMed] []
58. Klinger B, Jensen LT, Silbergeld A, et al. Insulin-like growth factor-I raises serum procollagen levels in children and adults with Laron syndrome. Clin Endocrinol 1996;45:423–9. [PubMed] []
59. Underwood LE, Backeljauw P. IGFs: function and clinical importance of therapy with recombinant human insulin-like growth factor I in children with insensitivity to growth hormone and in catabolic conditions. J Intern Med 1993;234:571–7. [PubMed] []
60. Ranke MB, Savage MO, Chatelain PG, et al. Long-term treatment of growth hormone insensitivity syndrome with IGF-I. Horm Res 1999;51:128–34. [PubMed] []
61. Ranke MB, Savage MO, Chatelain PG, et al. Insulin-like growth factor (IGF-I) improves height in growth hormone insensitivity: two years results. Horm Res 1995;44:253–64. [PubMed] []
62. Backeljauw PF, Underwood LE, The GHIS Collaborative Group. Prolonged treatment with recombinant insulin-like growth factor I in children with growth hormone insensitivity syndrome—a clinical research center study. J Clin Endocrinol Metab 1996;81:3312–17. [PubMed] []
63. Klinger B, Laron Z. Three year IGF-I treatment of children with Laron syndrome. J Pediatr Endocrinol Metab 1995;8:149–58. [PubMed] []
64. Guevara-Aguirre J, Rosenbloom AL, Vasconez O, et al. Two year treatment of growth hormone (GH) receptor deficiency with recombinant insulin-like growth factor-I in 22 children: comparison of two dosage levels and to GH treated GH deficiency. J Clin Endocrinol Metab 1997;82:629–33. [PubMed] []
65. Laron Z, Lilos P, Klinger B. Growth curves for Laron syndrome. Arch Dis Child 1993;68:768–70. [PMC free article] [PubMed] []
66. Krzisnik C, Battelino T. Five year treatment with IGF-I of a patient with Laron syndrome in Slovenia (a follow-up report). J Pediatr Endocrinol Metab 1997;10:443–7. [PubMed] []
67. Laron Z, Klinger B. Comparison of the growth-promoting effects of insulin-like growth factor I and growth hormone in the early years of life. Acta Paediatr 2000;89:38–41. [PubMed] []
68. Green H, Morikawa M, Nixon T. A dual effector theory of growth hormone action. Differentiation 1985;29:195–8. [PubMed] []
69. Ohlson C, Bengtsson BA, Isaksson OG, et al. Growth hormone and bone. Endocr Rev 1998;19:55–79. [PubMed] []
70. Maor G, Laron Z, Eshet R, et al. The early postnatal development of the murine mandibular condyle is regulated by endogenous insulin-like growth factor-I. J Endocrinol 1993;137:21–6. [PubMed] []
71. Sims NA, Clement-Lacroix P, Da Ponte F, et al. Bone homeostatis in growth hormone receptor-null mice is restored by IGF-I but independent of Stat5. J Clin Invest 2001;106:1095–103. [PMC free article] [PubMed] []

ℹ️ Basics: Cushing’s Syndrome vs Cushing’s Disease

MaryO Basic Info , , ,

What is Cushing’s syndrome?

Any condition that causes the adrenal gland to produce excessive cortisol results in the disorder Cushing’s syndrome. Cushing syndrome is characterized by facial and torso obesity, high blood pressure, stretch marks on the belly, weakness, osteoporosis, and facial hair growth in females.

Cushing’s syndrome has many possible causes including tumors within the adrenal gland, adrenal gland stimulating hormone (ACTH) produced from cancer such as lung cancer, and ACTH excessively produced from a pituitary tumors within the brain. ACTH is normally produced by the pituitary gland (located in the center of the brain) to stimulate the adrenal glands’ natural production of cortisol, especially in times of stress.

When a pituitary tumor secretes excessive ACTH, the disorder resulting from this specific form of Cushing’s syndrome is referred to as Cushing’s disease.

As an aside, it should be noted that doctors will sometimes describe certain patients with features identical to Cushing’s syndrome as having ‘Cushingoid’ features. Typically, these features are occurring as side effects of cortisone-related medications, such as prednisone and prednisolone.

❓Can You Help?

MaryO Can You Help? , , , , ,

Can someone please offer help, ive been suffering for a year and just got blood results today with a high cortisol reading. My doctor said that my contraceptive pill could have caused this, however, I am not on the regular pill but on the POP progesteron only pill.

Is anyone aware of if this raises cortisol levels the same way the regular combined pill does?

Any help would be so very much appreciated!

 

Please respond here, on the message boards, or in the original post.

 

Thanks!

❓Guest Question: Legal Assistance for Cushing’s Patients

MaryO Can You Help? , , , ,

 

If you can help, please respond here or on the Message Boards.  Thanks!

I believe I need legal assistance related to i humane treatment by city and/or county officials. I can explain further, if need be, once I find out if it’s even possible to get help. And I certainly cannot afford to pay an attorney, since my income is SSD (Disability), which is low and fixed, which has been the case since Cushing’s reared it’s remorseless, destructive head in 2008. Is there any legal assistance fund set up for Cushing’s patients?

 

🎬 Endoscopic Transsphenoidal Approach for Pituitary Tumor Resection

MaryO Uncategorized , , , , , , , , ,

Please be advised that this video contains graphic footage of surgery.

This video depicts an endoscopic transsphenoidal pituitary approach for a patient with a non-functioning macroadenoma. The surgery was performed by Dr. Garret Choby (Otolaryngology) and Dr. Jamie Van Gompel (Neurosurgery).

ℹ️ Basics: Testing: What Is a TSH Test?

MaryO Basic Info , , , , ,

A TSH test is done to find out if your thyroid gland is working the way it should. It can tell you if it’s overactive (hyperthyroidism) or underactive (hypothyroidism). The test can also detect a thyroid disorder before you have any symptoms. If untreated, a thyroid disorder can cause health problems.

TSH stands for “thyroid stimulating hormone” and the test measures how much of this hormone is in your blood. TSH is produced by the pituitary gland in your brain. This gland tells your thyroid to make and release the thyroid hormones into your blood.

The Test

The TSH test involves simply drawing some blood from your body. The blood will then be analyzed in a lab. This test can be performed at any time during the day. No preparation is needed (such as overnight fasting). You shouldn’t feel any pain beyond a small prick from the needle in your arm. You may have some slight bruising.

In general, there is no need to stop taking your medicine(s) before having your TSH level checked. However, it is important to let the doctor know what medications you are taking as some drugs can affect thyroid function. For example, thyroid function must be monitored if you are taking lithium. While taking lithium, there is a high chance that your thyroid might stop functioning correctly. It’s recommended that you have a TSH level test before starting this medicine. If your levels are normal, then you can have your levels checked every 6 to 12 months, as recommended by your doctor. If your thyroid function becomes abnormal, you should be treated.

High Levels of TSH

TSH levels typically fall between 0.4 and 4.0 milliunits per liter (mU/L), according to the American Thyroid Association. Ranges between laboratories will vary with the upper limit generally being between 4 to 5. If your level is higher than this, chances are you have an underactive thyroid.

In general, T3 and T4 levels increase in pregnancy and TSH levels decrease.

Low Levels of TSH

It’s also possible that the test reading comes back showing lower than normal levels of TSH and an overactive thyroid. This could be caused by:

Graves’ disease (your body’s immune system attacks the thyroid)

Too much iodine in your body

Too much thyroid hormone medication

Too much of a natural supplement that contains the thyroid hormone

If you’re on medications like steroids, dopamine, or opioid painkillers (like morphine), you could get a lower-than-normal reading. Taking biotin (B vitamin supplements) also can falsely give lower TSH levels.

The TSH test usually isn’t the only one used to diagnose thyroid disorders. Other tests, like the free T3, the free T4, the reverse T3, and the anti-TPO antibody, are often used too when determining whether you need thyroid treatment or not.

Treatment

Treatment for an underactive thyroid usually involves taking a synthetic thyroid hormone by pill daily. This medication will get your hormone levels back to normal, and you may begin to feel less tired and lose weight.

To make sure you’re getting the right dosage of medication, your doctor will check your TSH levels after 2 or 3 months. Once they are sure you are on the correct dosage, they will continue to check your TSH level each year to see whether it is normal.

If your thyroid is overactive, there are several options:

Radioactive iodine to slow down your thyroid

Anti-thyroid medications to prevent it from overproducing hormones

Beta blockers to reduce a rapid heart rate caused by high thyroid levels

Surgery to remove the thyroid (this is less common)

Your doctor may also regularly check your TSH levels if you have an overactive thyroid.

From https://www.webmd.com/women/what-is-tsh-test

ℹ️ Cushing’s Basics: The Endocrine System

MaryO Basic Info , , , ,

The endocrine system is a complex network of glands and organs. It uses hormones to control and coordinate your body’s metabolism, energy level, reproduction, growth and development, and response to injury, stress, and mood. The following are integral parts of the endocrine system:

 

  • Hypothalamus. The hypothalamus is located at the base of the brain, near the optic chiasm where the optic nerves behind each eye cross and meet. The hypothalamus secretes hormones that stimulate or suppress the release of hormones in the pituitary gland, in addition to controlling water balance, sleep, temperature, appetite, and blood pressure.
  • Pineal body. The pineal body is located below the corpus callosum, in the middle of the brain. It produces the hormone melatonin, which helps the body know when it’s time to sleep.
  •  Pituitary . The pituitary gland is located below the brain. Usually no larger than a pea, the gland controls many functions of the other endocrine glands.
  • Thyroid and parathyroid. The thyroid gland and parathyroid glands are located in front of the neck, below the larynx (voice box). The thyroid plays an important role in the body’s metabolism. The parathyroid glands play an important role in the regulation of the body’s calcium balance.
  • Thymus. The thymus is located in the upper part of the chest and produces white blood cells that fight infections and destroy abnormal cells.
  •  Adrenal gland . An adrenal gland is located on top of each kidney. Like many glands, the adrenal glands work hand-in-hand with the hypothalamus and pituitary gland. The adrenal glands make and release corticosteroid hormones and epinephrine that maintain blood pressure and regulate metabolism.
  •  Pancreas . The pancreas is located across the back of the abdomen, behind the stomach. The pancreas plays a role in digestion, as well as hormone production. Hormones produced by the pancreas include insulin and glucagon, which regulate levels of blood sugar.
  • Ovary. A woman’s ovaries are located on both sides of the uterus, below the opening of the fallopian tubes (tubes that extend from the uterus to the ovaries). In addition to containing the egg cells necessary for reproduction, the ovaries also produce estrogen and progesterone.
  • Testis. A man’s testes are located in a pouch that hangs suspended outside the male body. The testes produce testosterone and sperm.

❓Can You Help?

MaryO Can You Help? , , , , , ,

I think I have Cushing’s I have about 10 symptoms…my cortisol levels came out high with a 24 hour urine hormone panel but my endocrinologist did not even mention it. At the time when I had the test done, (March 2020)I had no idea what cortisol was. I just figured and trusted my endocrinologist would prescribe me with whatever hormones and or treatment I needed and would have me take whatever tests he order. Anyhow, in a range from 1-10 for bedtime cortisol, my result was 27! Cortisol metabolites, range from 1160-2183, my result was 5370!!!

The only reason I started to do more research on cortisol is because just a few weeks ago I started experiencing severe chest pain from the moment I wake up and any little thing stresses me out and gives me anxiety and I feel like I’m gonna have a heart attack any moment!  So I looked back at my paperwork and noticed these really elevated cortisol levels. But my endocrinologist never mention them… Why? This is how I found this disease,  I have so many symptoms of Cushing’s disease, And it is not a result of exogenous stuff causing cortisol levels to rise. I don’t take any medication whatsoever and was not taking any medication at that time or for the past year. All I have taken for the past year is what he prescribed, thyroid medication and progesterone. Someone please tell me if these levels are of concern from your perspective.

Please respond here or on the message boards.

Thanks!