Endocrine testing in obesity

Posted on March 20, 2021 by MaryO
John P H Wilding 1
Affiliations expand

Abstract

Endocrine disorders such as Cushing’s syndrome and hypothyroidism may cause weight gain and exacerbate metabolic dysfunction in obesity. Other forms of endocrine dysfunction, particularly gonadal dysfunction (predominantly testosterone deficiency in men and polycystic ovarian syndrome in women), and abnormalities of the hypothalamic-pituitary-adrenal axis, the growth hormone-IGF-1 system and vitamin D deficiency are common in obesity. As a result, endocrinologists may be referred people with obesity for endocrine testing and asked to consider treatment with various hormones. A recent systematic review and associated guidance from the European Society of Endocrinology provide a useful evidence summary and clear guidelines on endocrine testing and treatment in people with obesity. With the exception of screening for hypothyroidism, most endocrine testing is not recommended in the absence of clinical features of endocrine syndromes in obesity, and likewise hormone treatment is rarely needed. These guidelines should help reduce unnecessary endocrine testing in those referred for assessment of obesity and encourage clinicians to support patients with their attempts at weight loss, which if successful has a good chance of correcting any endocrine dysfunction.

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From https://pubmed.ncbi.nlm.nih.gov/32061161/

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8 medical conditions that could cause sudden weight gain

Posted on October 1, 2018 by MaryO

Weight gain can be associated with hormonal conditions, mood disorders, or other physiological factors. A sudden and unexplained weight gain could be your body’s way of signalling an underlying medical issue that needs to be addressed. For the sake of health and long-term well-being, it is important to differentiate between a few harmless extra kilos and a fluctuation that could be hiding a bigger problem. You can only be certain after consulting a healthcare practitioner.

If the weighing scale says your numbers are up but you haven’t changed your eating and exercise habits, you might consider any of the 8 medical conditions:

1.     Hypothyroidism The American Thyroid Association reveals that one in eight women will develop a thyroid disorder during her lifetime. Hypothyroidism refers to an underactive thyroid. The thyroid controls several body functions and your metabolism is one of them. If you’re not producing enough thyroid hormone your body can’t burn as much energy. Symptoms appear throughout your system. They include: weight gain, exhaustion, drier skin, thinner hair, bloating, muscle weakness, constantly feeling cold, and constipation. Once diagnosis is confirmed a doctor can prescribe an oral replacement for thyroid hormone that can relieve symptoms within weeks.

2.     Polycystic ovary syndrome (PCOS) One in 10 women of childbearing age undergoes PCOS. It is an endocrine disorder characterised by an imbalance in the sex hormones oestrogen and testosterone.  This results in irregular periods, acne and even facial hair growth. The disorder also disrupts the way the body uses insulin — which is the hormone responsible for converting carbohydrates into energy. As a result the sugars and starches you consume are stored as fat instead of energy, thus, weight gain. PCOS has no cure but women who have it can manage their symptoms with lifestyle changes and medication. A doctor’s consultation will help you find an appropriate method.

3. Insomnia Avoid fake news! Subscribe to the Standard SMS service and receive factual, verified breaking news as it happens. Text the word ‘NEWS’ to 22840 Sleep deprivation can negatively impact both your metabolism and your hunger hormones. Sleeping too little increases ghrelin, the hormone that signals the body that it’s time to eat, while lowering leptin, the hormone that says you are full. The result: increased cravings and snacking to get more energy through the day. Insomnia increases impulsive eating. A 2018 study published in the American Journal of Clinical Nutrition found that the right amount of sleep could mean consuming up to 10 fewer grams of sugar throughout the day.

4.     Tumours Weight gain around your belly as opposed to your lower body or other areas can be more dangerous to your health. Large pelvic area tumours like uterine or ovarian tumours can inflate the abdomen the way excess fat does. In some cases they can also be cancerous. In addition to weight gain, symptoms of ovarian or uterine tumours include vaginal bleeding, lower back pain, constipation and painful intercourse. But these signs are common for other conditions as well so it‘s worth confirming with a doctor to rule out any possible complications.

5. Peri menopause and menopause Perimenopause -the transition period to menopause can start as early as a woman’s mid-thirties, but usually starts in their forties. This period triggers hormones like oestrogen to rise and fall unevenly, which can cue weight gain in some women. Genetics are a good starting point on how your body experiences these changes, so it would be helpful to look into how it affected your mother and other older women in your family. Other signs of perimenopause are mood swings, irregular periods, hot flashes, and changes in libido. Age also contributes to loss of muscle mass and increase in body fat. An Ob-Gyn should be able to talk you through these changes and recommend management options.

6.     Mood disorders Depression and anxiety can result in fatigue, lack of focus and irritability. Some people cope with anxious or sad feelings by mindlessly munching on food they don’t really need. Additionally chronic stress throws your body into fight-or-flight mode, leading to a surge of adrenaline, as well as a heavy dose of the hormone cortisol –responsible for restoring energy reserves and storing fat.

7. Cushing syndrome Sometimes tumours on the pituitary or adrenal glands can contribute to a condition known as Cushing’s disease which is characterised by high levels of cortisol in the blood. Taking long term steroids could also result in this disease. Patients with Cushing syndrome will experience rapid weight gain in the face, abdomen and chest. They also display slender arms and legs compared to the heavy weight in the core of the body. Other symptoms include: high blood pressure, mood swings, osteoporosis, discoloured stretch marks, acne, and fragile skin. Depending on the cause, Cushing‘s disease can be treated in a different ways.

8. New medication Before starting on any new prescription medication, ask your doctor if weight gain is a possible side effect. Birth control pills may lead to weight gain depending on the brand, dosage, and the person’s hormonal levels. Psychiatric medications, especially for depression and bipolar disorder, have been known to cause weight gain, as they target the brain. Similarly, taking insulin to manage diabetes or medications that treat high blood pressure can also lead to extra kilos, so staying active and sticking to a strict meal plan can help you take insulin without unnecessarily weight gain.

Adapted from https://www.standardmedia.co.ke/lifestyle/article/2001297348/8-medical-conditions-that-could-cause-sudden-weight-gain

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Cushing’s Syndrome: A Tale of Frequent Misdiagnosis

Posted on June 24, 2017 by MaryO
by Jessica Rotham, National Center for Health Research

What is it?

Cushing’s syndrome is a condition you probably have never heard of, but for those who have it, the symptoms can be quite scary.  Worse still, getting it diagnosed can take a while.  Cushing’s syndrome occurs when the tissues of the body are exposed to high levels of cortisol for an extended amount of time. Cortisol is the hormone the body produces to help you in times of stress. It is good to have cortisol at normal levels, but when those levels get too high it causes health problems.  Although cortisol is related to stress, there is no evidence that Cushing’s syndrome is directly or indirectly caused by stress.

Cushing’s syndrome is considered rare, but that may be because it is under-reported. As a result, we don’t have good estimates for how many people have it, which is why the estimates for the actual number of cases vary so much–from 5 to 28 million people.[1] The most common age group that Cushing’s affects are those 20 to 50 years old.  It is thought that obesity, type 2 diabetes, and high blood pressure may increase your risk of developing this syndrome.[2]

What causes Cushing’s Syndrome?

Cushing’s syndrome is caused by high cortisol levels. Cushing’s disease is a specific form of Cushing’s syndrome. People with Cushing’s disease have high levels of cortisol because they have a non-cancerous (benign) tumor in the pituitary gland.  The tumor releases adrenocorticotropin hormone (ACTH), which causes the adrenal glands to produce excessive cortisol.

Cushing’s syndrome that is not Cushing’s disease can be also caused by high cortisol levels that result from tumors in other parts of the body.  One of the causes is “ectopic ACTH syndrome.” This means that the hormone-releasing tumor is growing in an abnormal place, such as the lungs or elsewhere.  The tumors can be benign, but most frequently they are cancerous. Other causes of Cushing’s syndrome are benign tumors on the adrenal gland (adrenal adenomas) and less commonly, cancerous adrenal tumors (adrenocortical carcinomas). Both secrete cortisol, causing cortisol levels to get too high.

In some cases, a person can develop Cushing’s syndrome from taking steroid medications, such as prednisone. These drugs, known as corticosteroids, mimic the cortisol produced by the body. People who have Cushing’s syndrome from steroid medications do not develop a tumor.[3]

What are the signs and symptoms of Cushing’s Syndrome?

The appearance of people with Cushing’s syndrome starts to change as cortisol levels build up. Regardless of what kind of tumor they have or where the tumor is located, people tend to put on weight in the upper body and abdomen, with their arms and legs remaining thin; their face grows rounder (“moon face”); they develop fat around the neck; and purple or pink stretch marks appear on the abdomen, thighs, buttocks or arms. Individuals with the syndrome usually experience one or more of the following symptoms: fatigue, muscle weakness, high glucose levels, anxiety, depression, and high blood pressure. Women are more likely than men to develop Cushing’s syndrome, and when they do they may have excess hair growth, irregular or absent periods, and decreased fertility.[4]

Why is Cushing’s Syndrome so frequently misdiagnosed?

These symptoms seem distinctive, yet it is often difficult for those with Cushing’s syndrome to get an accurate diagnosis.  Why?  While Cushing’s is relatively rare, the signs and symptoms are common to many other diseases. For instance, females with excess hair growth, irregular or absent periods, decreased fertility, and high glucose levels could have polycystic ovarian syndrome, a disease that affects many more women than Cushing’s.   Also, people with metabolism problems (metabolic syndrome), who are at higher than average risk for diabetes and heart disease, also tend to have abdominal fat, high glucose levels and high blood pressure.[5]

Problems in testing for Cushing’s

When Cushing’s syndrome is suspected, a test is given to measure cortisol in the urine. This test measures the amount of free or unbound cortisol filtered by the kidneys and then released over a 24 hour period through the urine. Since the amount of urinary free cortisol (UFC) can vary a lot from one test to another—even in people who don’t have Cushing’s—experts recommend that the test be repeated 3 times. A diagnosis of Cushing’s is given when a person’s UFC level is 4 times the upper limit of normal.  One study found this test to be highly accurate, with a sensitivity of 95% (meaning that 95% of people who have the disease will be correctly diagnosed by this test) and a specificity of 98% (meaning that 98% of  people who do not have the disease will have a test score confirming that).[6] However, a more recent study estimated the sensitivity as only between 45%-71%, but with 100% specificity.[7]  This means that the test is very accurate at telling people who don’t have Cushing’s that they don’t have it, but not so good at identifying the people who really do have Cushing’s.  The authors that have analyzed these studies advise that patients use the UFC test together with other tests to confirm the diagnosis, but not as the initial screening test.[8]  

Other common tests that may be used to diagnose Cushing’s syndrome are: 1) the midnight plasma cortisol and late-night salivary cortisol measurements, and 2) the low-dose dexamethasone suppression test (LDDST).  The first test measures the amount of cortisol levels in the blood and saliva at night.  For most people, their cortisol levels drop at night, but people with Cushing’s syndrome have cortisol levels that remain high all night. In the LDDST, dexamethasone is given to stop the production of ACTH.  Since ACTH produces cortisol, people who don’t have Cushing’s syndrome will get lower cortisol levels in the blood and urine. If after giving dexamethasone, the person’s cortisol levels remain high, then they are diagnosed with Cushing’s.[9]

Even when these tests, alone or in combination, are used to diagnose Cushing’s, they don’t explain the cause. They also don’t distinguish between Cushing’s syndrome, and something called pseudo-Cushing state.

Pseudo-Cushing state

Some people have an abnormal amount of cortisol that is caused by something unrelated to Cushing’s syndrome such as polycystic ovarian syndrome, depression, pregnancy, and obesity. This is called pseudo-Cushing state.  Their high levels of cortisol and resulting Cushing-like symptoms can be reversed by treating whatever disease is causing the abnormal cortisol levels. In their study, Dr. Giacomo Tirabassi and colleagues recommend using the desmopressin (DDAVP) test to differentiate between pseudo-Cushing state and Cushing’s.  The DDAVP test is especially helpful in people who, after being given dexamethasone to stop cortisol production, continue to have moderate levels of urinary free cortisol (UFC) and midnight serum cortisol.[10]

An additional test that is often used to determine if one has pseudo-Cushing state or Cushing’s syndrome is the dexamethasone-corticotropin-releasing hormone (CRH) test. Patients are injected with a hormone that causes cortisol to be produced while also being given another hormone to stop cortisol from being produced. This combination of hormones should make the patient have low cortisol levels, and this is what happens in people with pseudo-Cushing state.  People with Cushing’s syndrome, however, will still have high levels of cortisol after being given this combination of hormones.[11]

How can Cushing’s be treated?

Perhaps because Cushing’s is rare or under-diagnosed, few treatments are available. There are several medications that are typically the first line of treatment.  None of the medications can cure  Cushing’s, so they are usually taken until other treatments are given to cure Cushing’s, and only after that if the other treatment fails.

The most common treatment for Cushing’s disease is transsphenoidal surgery, which requires the surgeon to reach the pituitary gland through the nostril or upper lip and remove the tumor.  Radiation may also be used instead of surgery to shrink the tumor.  In patients whose Cushing’s is caused by ectopic ACTH syndrome, all cancerous cells need to be wiped out through surgery, chemotherapy, radiation or a variety of other methods, depending on the location of the tumor. Surgery is also recommended for adrenal tumors.  If Cushing’s syndrome is being caused by corticosteroid (steroid medications) usage, the treatment is to stop or lower your dosage.[12]

Medications to control Cushing’s (before treatment or if treatment fails)

According to a 2014 study in the Journal of Clinical Endocrinology and Metabolism, almost no new treatment options have been introduced in the last decade. Researchers and doctors have focused most of their efforts on improving existing treatments aimed at curing Cushing’s. Unfortunately, medications used to control Cushing’s prior to treatment and when treatment fails are not very effective.

Many of the medications approved by the FDA for Cushing’s syndrome and Cushing’s disease, such as pasireotide, metyrapone, and mitotane, have not been extensively studied.  The research presented to the FDA by the makers of these three drugs did not even make clear what an optimal dose was.[13] In another 2014 study, published in Clinical Epidemiology, researchers examined these three same drugs, along with ten others, and found that only pasireotide had moderate evidence to support its approval.  The other drugs, many of which are not FDA approved for Cushing’s patients, had little or no available evidence to show that they work.[14] They can be sold, however, because the FDA has approved them for other diseases.  Unfortunately, that means that neither the FDA nor anyone else has proven the drugs are safe or effective for Cushing patients.

Pasireotide, the one medication with moderate evidence supporting its approval, caused hyperglycemia (high blood sugar) in 75% of patients who participated in the main study for the medication’s approval for Cushing’s.  As a result of developing hyperglycemia, almost half (46%) of the participants had to go on blood-sugar lowering medications. The drug was approved by the FDA for Cushing’s anyway because of the lack of other effective treatments.

Other treatments used for Cushing’s have other risks.  Ketoconazole, believed to be the most commonly prescribed medications for Cushing’s syndrome, has a black box warning due to its effect on the liver that can lead to a liver transplant or death.  Other side effects include: headache, nausea, irregular periods, impotence, and decreased libido. Metyrapone can cause acne, hirsutism, and hypertension. Mitotane can cause neurological and gastrointestinal symptoms such as dizziness, nausea, and diarrhea and can cause an abortion in pregnant women.[15]

So, what should you do if you suspect you have Cushing’s Syndrome?

Cushing’s syndrome is a serious disease that needs to be treated, but there are treatment options available for you if you are diagnosed with the disease. If the symptoms in this article sound familiar, it’s time for you to go see your doctor. Make an appointment with your general practitioner, and explain your symptoms to him or her.  You will most likely be referred to an endocrinologist, who will be able to better understand your symptoms and recommend an appropriate course of action.

 

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

  1. Nieman, Lynette K. Epidemiology and clinical manifestations of Cushing’s syndrome, 2014. UpToDate: Wolters Kluwer Health
  2. Cushing’s syndrome/ disease, 2013. American Association of Neurological Surgeons. http://www.aans.org/Patient%20Information/Conditions%20and%20Treatments/Cushings%20Disease.aspx
  3. Cushing’s syndrome, 2012. National Endocrine and Metabolic Diseases: National Institutes of Health. http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#treatment
  4. Cushing’s syndrome, 2012. National Endocrine and Metabolic Diseases: National Institutes of Health. http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#treatment
  5. Cushing’s syndrome, 2012. National Endocrine and Metabolic Diseases: National Institutes of Health. http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#treatment
  6. Newell-Price, John, Peter Trainer, Michael Besser and Ashley Grossman. The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states, 1998. Endocrine Reviews: Endocrine Society
  7. Carroll, TB and JW Findling. The diagnosis of Cushing’s syndrome, 2010. Reviews in Endocrinology and Metabolic Disorders: Springer
  8. Ifedayo, AO and AF Olufemi. Urinary free cortisol in the diagnosis of Cushing’s syndrome: How useful?, 2013. Nigerian Journal of Clinical Practice: Medknow.
  9. Cushing’s syndrome, 2012. National Endocrine and Metabolic Diseases: National Institutes of Health. http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#treatment
  10. Tirabassi, Giacomo, Emanuela Faloia, Roberta Papa, Giorgio Furlani, Marco Boscaro, and Giorgio Arnaldi. Use of the Desmopressin test in the differential diagnosis of pseudo-Cushing state from Cushing’s disease, 2013. The Journal of Clinical Endocrinology & Metabolism: Endocrine Society.
  11. Cushing’s syndrome, 2012. National Endocrine and Metabolic Diseases: National Institutes of Health. http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#treatment
  12. Cushing’s syndrome, 2012. National Endocrine and Metabolic Diseases: National Institutes of Health. http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#treatment
  13. Tirabassi, Giacomo, Emanuela Faloia, Roberta Papa, Giorgio Furlani, Marco Boscaro, and Giorgio Arnaldi. Use of the Desmopressin test in the differential diagnosis of pseudo-Cushing state from Cushing’s disease, 2013. The Journal of Clinical Endocrinology & Metabolism: Endocrine Society.
  14. Galdelha, Monica R. and Leonardo Vieira Neto. Efficacy of medical treatment in Cushing’s disease: a systematic review, 2014. Clinical Endocrinology: John Wiley & Sons.
  15. Adler, Gail. Cushing syndrome treatment & management, 2014. MedScape: WebMD.

Adapted from https://www.center4research.org/cushings-syndrome-frequent-misdiagnosis/

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Pituitary Issues: Irregular Periods

Posted on February 1, 2017 by MaryO

Q: I am 28 years old and I have not yet started my periods naturally. I have to take medicine for periods — Novelon. The doctors say that there is some problem with my hormones in the pituitary gland. Please advise me how to get normal and natural periods, because after taking the medicine I get my period, but without medicines I don’t.

A by Dr Sharmaine Mitchell: The problem you have with your menstrual period being irregular is most likely due to overproduction of the hormone prolactin by the pituitary gland in the brain. The pituitary gland can sometimes enlarge and cause an overproduction of prolactin and this can result in inappropriate milk production in the breasts (white nipple discharge), irregular menstruation or absent menstrual periods, headaches and blurred vision. The blurred vision occurs as a result of compression of the optic nerve which supplies the eyes, by the enlarged brain tumour in the pituitary gland.

You should get a magnetic resonance imaging (MRI) or CT scan of the brain and pituitary gland done. You should also test your prolactin levels to determine the extent of overproduction of the hormone.

Other investigations should include a thyroid function test (TSH), follicle stimulating hormone (FSH) and leutinizing hormone (LH), and baseline testosterone level tests.

Abnormalities in the production of thyroid hormones can also cause menstrual irregularities and this should be ruled out.

Polycystic ovarian disease can also cause irregular menstrual periods and checking the level of FSH, LH and testosterone will help to rule out this diagnosis. This condition is usually associated with excessive weight gain, abnormal male pattern distribution on the face, chest and abdomen and an increased risk for diabetes mellitus. A pelvic ultrasound to look at the structure of the ovaries and to rule out polycystic ovaries is essential.

If the pituitary gland is enlarged, then medication can be prescribed to shrink it. Bromocriptine or Norprolac are commonly used drugs which work well in reducing the prolactin levels and establishing regular menstrual cycles. The use of these drugs will also help to establish ovulation and improve your fertility.

In some cases it may become necessary to have surgery done if the tumour in the pituitary gland is large and does not respond to the usual medications prescribed to shrink the pituitary gland. The MRI of the brain and pituitary gland will give an idea as to the size of the gland and help to determine if there is a need for you to see the neurosurgeon.

In most cases medical management with drugs will work well and there is no need for surgical intervention. This is a problem that can recur, so it may be necessary to take treatment intermittently for a long period of time, especially if fertility is desired.

Consult your doctor who will advise you further. Best wishes.

Dr Sharmaine Mitchell is an obstetrician and gynaecologist. Send questions via e-mail to allwoman@jamaicaobserver.com; write to All Woman, 40-42 1/2 Beechwood Ave, Kingston 5; or fax to 968-2025. All responses are published. Dr Mitchell cannot provide personal responses.

DISCLAIMER:

The contents of this article are for informational purposes only and must not be relied upon as an alternative to medical advice or treatment from your own doctor.

From http://www.jamaicaobserver.com/magazines/allwoman/Still-no-normal-period-at-28_87596

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Cushing’s Syndrome Epidemiology

Posted on August 3, 2016 by MaryO

By Yolanda Smith, BPharm

Cushing’s syndrome is considered to be a rare disorder that results from prolonged exposure to glucocorticoids. However, there are few epidemiological studies to provide adequate data to describe the incidence and prevalence of the condition accurately. Most cases are diagnosed between the ages of 20 and 50, although any individual may be affected at any age.

The presentation of the symptoms of Cushing’s syndrome can vary greatly. In addition, many of the symptoms overlap with those caused by other health conditions, such as metabolic syndrome and polycystic ovary syndrome. This can make the diagnosis of the condition difficult. It is also difficult to establish epidemiological trends in Cushing’s syndrome, because not all cases of the disease are diagnosed. However, it is important that diagnosis is made as soon as possible, because early diagnosis and treatment of the condition are associated with improved morbidity and mortality rates.

Population-based Studies

There are several population-based studies that have reported the incidence and mortality rates of Cushing’s syndrome in certain populations over a discrete period of time.

A study in Denmark followed 166 patients with Cushing’s syndrome for 11 years, finding an incidence of 2 cases per million population per year. Of the 166 patients, 139 had benign disease. There was a mortality rate of 16.5% in the follow-up period of 8 years, with most deaths occurring in the year after the initial diagnosis, often before the initiation of treatment. The causes of death of patients with Cushing’s syndrome in the study included severe infections, cardiac rupture, stroke and suicide.

A study in Spain found 49 cases of Cushing’s syndrome over a period of 18 years, with an incidence of 2.4 cases per million inhabitants per year and a prevalence of 39.1 cases per million. The standard mortality ratio in this study was 3.8, in addition to an increase in morbidity rates.

Incidence

A low incidence of endogenous Cushing’s syndrome was established by the population-based studies outlined above, corresponding to approximately 2 cases per million. Some studies have an estimated incidence as low as 0.7 people per million.

However, the incidence of subclinical Cushing’s syndrome may be underestimated in certain population groups, such as those with osteoporosis, uncontrolled diabetes mellitus or hypertension. For example, of 90 obese patients with uncontrolled diabetes mellitus in one study, three had Cushing’s syndrome. This yielded a prevalence of 3.3%, which is considerably higher than the incidence reported in the population-based studies. However, these findings should be supported by larger studies.

Females are more likely to be affected by Cushing’s syndrome than males, with a risk ratio of approximately 3:1. There does not appear to be a genetic link that involves an ethnic susceptibility to the condition.

Treatment Outcomes

Surgery is the first-line treatment option for most cases of overt disease and remission is achieved in the majority of patients, approximately 65-85%. However, for up to 1 in 5 patients the condition recurs, and the risk does not appear to level off, even after 20 years of follow-up.

The risk of mortality for individuals with Cushing’s syndrome is estimated to be 2-3 times higher than that of the general population, based on epidemiological studies.

Reviewed by Dr Liji Thomas, MD.

From http://www.news-medical.net/health/Cushings-Syndrome-Epidemiology.aspx

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