Researchers Report Rare Case of Cushing’s Caused by Bilateral Adrenal Tumors

Cases of adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome are often caused by unilateral tumors in the adrenal glands, but Indian researchers have now reported a rare case where the condition was caused by tumors in both adrenal glands.

Fewer than 40 cases of bilateral tumors have been reported so far, but an accurate diagnosis is critical for adequate and prompt treatment. Sampling the veins draining the adrenal glands may be a good way to diagnose the condition, researchers said.

The study, “Bilateral adrenocortical adenomas causing adrenocorticotropic hormone-independent Cushing’s syndrome: A case report and review of the literature,” was published in the World Journal of Clinical Cases.

Cushing’s syndrome, a condition characterized by excess cortisol in circulation, can be divided into two main forms, depending on ACTH status. Some patients have tumors that increase the amount of ACTH in the body, and this hormone will act on the adrenal glands to produce cortisol in excess. Others have tumors in the adrenal glands, which produce excess cortisol by themselves, without requiring ACTH activation. This is known as ACTH-independent Cushing’s syndrome.

Among the latter, the disease is mostly caused by unilateral tumors — in one adrenal gland only —  with cases of bilateral tumors being extremely rare in this population.

Now, researchers reported the case of a 31-year-old Indian woman who developed ACTH-independent Cushing’s syndrome because of tumors in both adrenal glands.

The patient complained of weight gain, red face, moon face, bruising, and menstrual irregularity for the past two years. She recently had been diagnosed with high blood pressure and had started treatment the month prior to the presentation.

A physical examination confirmed obesity in her torso, moon face, buffalo hump, thin skin, excessive hair growth, acne, swollen legs and feet, and skin striae on her abdomen, arms, and legs.

Laboratory examinations showed that the woman had an impaired tolerance to glucose, excess insulin, and elevated cortisol in both the blood and urine. Consistent with features of Cushing’s syndrome, cortisol levels had no circadian rhythm and were non-responsive to a dexamethasone test, which in normal circumstances lowers cortisol production.

Because ACTH levels were within normal levels, researchers suspected an adrenal tumor, which led them to conduct imaging scans.

An abdominal computed tomography (CT) scan showed adrenal adenomas in both adrenal glands (right: 3.1 cm × 2.0 cm × 1.9 cm; left: 2.2 cm × 1.9 cm × 2.1 cm). A magnetic resonance imaging (MRI) scan showed that the pituitary gland (which normally produces ACTH) was normal.

To determine whether both adrenal tumors were producing cortisol, researchers sampled the adrenal veins and compared their cortisol levels to those of peripheral veins. They found that the left adrenal gland was producing higher amounts of cortisol, thought the right adrenal gland was also producing cortisol in excess.

“Our case indicates that adrenal vein [blood] sampling might be useful for obtaining differential diagnoses” in cases of Cushing’s syndrome, researchers stated. Also, they may help design a surgical plan that makes much more sense.”

The tumors were surgically removed — first the left, and three months later the right — which alleviated many of her symptoms. She also started prednisolone treatment, which helped resolve many disease symptoms.

“Bilateral cortisol-secreting tumors are a rare cause of Cushing’s syndrome,” researchers said. So when patients present bilateral adrenal lesions, “it is crucial to make a definitive diagnosis before operation since various treatments are prescribed for different causes,” they said.

The team recommends that in such cases the two tumors should not be removed at the same time, as this approach may cause adrenal insufficiency and the need for glucocorticoid replacement therapy.

From https://cushingsdiseasenews.com/2019/06/27/rare-case-of-cs-due-to-bilateral-tumors-in-the-adrenal-glands/

Post-traumatic Stress Symptoms Common in Cushing’s Patients Before Surgery

Patients with Cushing’s disease may develop post-traumatic stress symptoms, which are generally resolved once they undergo surgery to remove the tumor, but can persist in some cases, a study shows.

The study, “Posttraumatic stress symptoms (PTSS) in patients with Cushing’s disease before and after surgery: A prospective study,” was published in the Journal of Clinical Neuroscience.

Cushing’s disease is an endocrine disorder characterized by excess secretion of the adrenocorticotropic hormone (ACTH) by a pituitary adenoma (tumor of the pituitary gland). This leads to high levels of cortisol, a condition known as hypercortisolism.

Chronic hypercortisolism is associated with symptoms such as central obesity, buffalo hump, body bruising, muscle weakness, high blood pressure, high blood sugar, and weak bones.

Additionally, patients can develop psychiatric disorders including depression, anxiety, and cognitive dysfunction, all of which contribute considerably to a lower health-related quality of life.

Depression and anxiety rates are particularly high in Cushing’s disease patients, with 54% of them experiencing major depression and 79% having anxiety.

Due to the significant impact of psychological factors in these patients, they may be susceptible to post-traumatic stress symptoms (PTSS). But more information on this phenomenon in these patients is still needed.

To address this lack of data, a group of Chinese researchers conducted a prospective study to investigate the occurrence, correlated factors, and prognosis of PTSS in patients with Cushing’s disease.

A total of 49 patients newly diagnosed with Cushing’s disease who underwent transsphenoidal removal of the tumor as their first-line treatment were asked to participate in this study. Another group of 49 age- and sex-matched healthy individuals were included as controls.

PTSS was measured using the Impact of Event Scale-Revised (IES-R), depression/anxiety were measured using the Hospital Anxiety and Depression scale (HADS), and quality of life was measured using the 36-item short-form (SF-36). These parameters were measured before surgery, and then at six and 12 months after the procedure.

Before surgery, 15 patients (30.6%) had PTSS. These patients also had higher cortisol levels, worse levels of depression/anxiety, and worse quality of life scores than those without PTSS.

While most of the patients recovered after the operation, there were five (33.3%) for whom PTSS persisted for more than a year.

Additionally, one patient who had a recurrence of Cushing’s disease developed PTSS between six and 12 months after the first surgery.

PTSS severity showed consistent improvement after surgery, which was correlated with better depression/anxiety scores and psychological aspects of the SF-36. However, Cushing’s disease patients in remission still performed worse than healthy individuals concerning their physical and mental health.

Therefore, “patients with [Cushing’s disease] can develop PTSS, and they may persist for over a year even after successful surgery. Combined psychological intervention is advised for these patients,” the researchers concluded.

From https://cushingsdiseasenews.com/2019/06/25/cushings-patients-often-have-post-traumatic-stress-symptoms

Cushing’s Patient Exhibits Cortisol-Secreting Lesions in Both Adrenal Glands

In rare cases, Cushing’s syndrome may be caused by cortisol-secreting masses in both adrenal glands, a case report shows.

The study with that finding, “ACTH-independent Cushing’s syndrome with bilateral cortisol-secreting adrenal adenomas: a case report and review of literatures” was published in BMC Endocrine Disorders.

Cushing’s syndrome results from the prolonged secretion of excess cortisol. While most cases are caused by tumors in the pituitary gland, up to 20 percent result from tumors in the adrenal glands.

Occasionally, Cushing’s syndrome is caused by masses in both adrenal glands, which may be similar or display different properties. “Determining the nature and function of bilateral adrenal masses is always a challenge in clinical practice,” researchers said.

Now, physicians at Sichuan University in China, reported the case of a 55-year-old woman who complained of difficulty breathing for more than 10 years.

The patient had developed obesity of the trunk and face over the past two years, and had been diagnosed with hypertension 10 years before. She also had high lipid levels for the past five years.

The patient was taking Avapro (irbesartan), Lopressor (metoprolol), Procardia XL (nifedipine), and statins for these disorders. No other health conditions or treatments were reported.

Physical examination showed a moon-shaped face, truncal obesity, and accumulation of fat in the back of the neck and upper back (aka buffalo hump). She also had discoloration of the lower limbs, with slight fluid accumulation and muscle weakness.

Routine blood analysis did not reveal significant changes, but hormone analysis showed high cortisol levels and low adrenocorticotropic hormone (ACTH) was low.

The amount of 24-hour urine-free cortisol was almost five times higher than the upper normal limit. Also, the patients had reduced response to corticosteroids treatment, showing even higher cortisol levels upon treatment with 1 mg dexamethasone. Additional evaluations revealed reduced bone mineral density, indicative of osteoporosis.

Together, the findings led to a diagnosis of ACTH-independent Cushing’s syndrome.

To identify what was causing Cushing’s syndrome, the team looked at the adrenal glands. They detected three lesions, one on the right side measuring 2.5 centimeters, and two on the left side, with 2.3 cm and 0.6 cm respectively. The masses in both sides were actively producing cortisol in similar proportions.

These results confirmed that the patient had Cushing’s syndrome induced by bilateral adrenal excessive cortisol secretion.

Because the patient had poor cardiac function, researchers planned a two-step operation. First, they removed the right adrenal gland laparoscopically, followed by the left adrenal gland two months later. The patient started replacement therapy with hydrocortisone, and her cortisol levels improved significantly, returning to normal levels. She also lost 4 kilograms (8.8 pounds) of body weight in the following year.

“The optimal treatment for patients with bilateral cortisol-secreting adenomas remains uncertain,” the researchers wrote. Although there are no reports of recurrence after surgical treatment, the long-term outcome of these patients remains unclear, and “lifelong follow-up of the patient is required,” they added.

Bilateral cortisol-secreting adrenal adenomas are rare, having been reported in only 15 other studies, the team wrote. Interestingly, some features reported in this study also were identified by other researchers, including the fact that bilateral cortisol-secreting adrenal lesions are more predominantly found in females during adulthood. Also, the size of the lesions commonly range between 1 to 5 centimeters when detected, and appear at approximately the same time in both adrenal glands.

Although there are no treatment guidelines for these cases, surgical removal of the lesions or adrenal glands, plus glucocorticoid replacement therapy, is the mostly used therapeutic approach. Importantly, the researchers noted that patients who underwent partial gland removal were able to withdraw from glucocorticoid replacement therapy during follow-up.

From https://cushingsdiseasenews.com/2018/05/03/cushings-patient-has-cortisol-secreting-lesions-in-both-adrenal-glands/

Cushing’s and Hairy Nipples

Hairy nipples are a common condition in women. The amount of hair on the nipples varies, but some women find that the hair becomes long, coarse, and dark, which can be distressing.

Hairy nipples are rarely a cause for concern and are usually not a sign of any underlying health issues. However, occasionally they can signify something more serious, in which case, it is essential to consult a doctor.

Almost every part of a person’s skin is covered in hair and hair follicles. On certain parts of the body, such as the top of the head, the hair usually grows longer and thicker, while on other parts, it is thin and transparent.

Fast facts on hairy nipples:

  • It is not known how common hairy nipples are or how many women have them.
  • Many women do not report the condition and instead manage it themselves.
  • It is possible for hair that used to be fine and light to turn coarse and dark with age.

Causes of hairy nipples in women

There are several underlying reasons that might cause nipple hairs to grow. These are:

Cushing’s syndrome

Cushing’s syndrome is another condition caused by hormonal imbalance. When it occurs, there is an excess of cortisol in the body. In this case, a person may experience several symptoms, such as:

  • increased hair growth
  • abnormal menstrual periods
  • high blood pressure
  • a buildup of fat on the chest and tummy, while arms and legs remain slim
  • a buildup of fat on the back of the neck and shoulders
  • a rounded and red, puffy face
  • bruising easily
  • big purple stretch marks
  • weakness in the upper arms and thighs
  • low libido
  • problems with fertility
  • mood swings
  • depression
  • high blood glucose level

Cushing’s syndrome is fairly rare, and the cause is usually associated with taking glucocorticosteroid medicine, rather than the body overproducing the hormone on its own.

It is possible, however, that a tumor in the lung, pituitary gland, or adrenal gland is the cause.

Also:

Hormonal changes and fluctuations

Hormonal changes in women can cause many different symptoms, one of which is changes in nipple hair growth and color.

Some common hormonal changes happen during pregnancy and menopause.

However, hormonal changes can also occur when a woman is in her 20s and 30s, which may cause nipple hair to change appearance or become noticeable for the first time.

Overproduction of male hormones

It is possible for hormonal imbalances to cause hairy nipples. Overproduction of male hormones, including testosterone, can cause hair growth, while other symptoms include:

  • oily skin that can lead to breakouts and acne
  • menstrual periods stopping
  • increase in skeletal muscle mass
  • male pattern baldness, leading to a woman losing hair on her head

If overproduction of male hormones is suspected, it is a good idea to make an appointment with a doctor who can confirm this with a simple test.

Polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) occurs because of a hormonal imbalance. PCOS is a condition that affects the way the ovaries work.

Common symptoms of PCOS are:

  • infertility
  • irregular menstrual periods
  • ovarian cysts
  • excessive hair growth in unusual places, such as the nipples

PCOS is believed to affect around 1 in 5 women.

Medication

The side effects of particular medicines can cause unusual hair growth.

Medicines, such as testosterone, glucocorticosteroids, and certain other immunotherapy drugs may cause hairy nipples.

What are the treatment options?

Treatment for hairy nipples is not usually necessary for health reasons.

However, many women with the condition prefer to try and reduce or get rid of the appearance of hair on their nipples for cosmetic purposes.

There are several methods by which they can try and do this:

Trimming the nipple hair

Trimming the nipple hair may be enough to reduce its appearance. Small nail scissors are ideal, and hair can be cut close to the skin. It is essential to do this carefully and avoid catching the skin.

Trimming will need to be carried out regularly when the hair grows back.

Tweezing the nipple hair

Tweezing nipple hair is an effective way to get rid of unwanted nipple hair. However, this option can be painful as the skin around the nipple area is particularly soft and sensitive.

It is also important to bear in mind that the hair will return, and tweezing the hair increases the risk of infection and ingrown hairs.

Shaving the nipple hair

Shaving is another option to reduce the appearance of nipple hair. However, it is advisable to do so with caution to avoid nicking the sensitive skin.

This option also carries an increased risk of developing ingrown hairs and infection.

Waxing

Sugaring or waxing is a good hair removal option, though either one is likely to be painful. A salon is the best place to get this treatment type, as doing this at home may cause damage to the skin. Infection and ingrown hairs are again a risk.

Laser hair removal

These popular treatments can help to reduce the hair growth and slow or even prevent regrowth for a while. However, they can be painful, too.

Laser treatment is by far the most expensive option, as it will need to be performed by a plastic surgeon or cosmetic dermatologist.

Hormonal treatment

If a hormonal imbalance is the cause of hairy nipples, a doctor may prescribe or adjust a woman’s medication therapy to restore a healthy hormonal balance.

Other treatments and how to choose

The above treatments are all commonly used to remove and reduce nipple hair and usually have minimal side effects.

Bleaching or using hair removal cream to treat the condition, however, is not advised as these methods are usually too harsh for this sensitive area and may cause irritation and damage.

At what point should you see a doctor?

Hairy nipples in women are quite common, and there is usually no need to see a doctor. However, if they are accompanied by any other unusual symptoms, it is a good idea to make an appointment.

A doctor will be able to perform tests to determine whether an underlying cause, such as PCOS, is causing the growth of nipple hair. If so, they will give advice and medication therapy to help manage the condition.

A doctor will also be able to advise how to remove nipple hair safely.

Takeaway

For the majority of women, nipple hair may seem unsightly, but it is not a cause for any concerns about their health.

However, because some medical conditions can cause nipple hair to darken and grow, it is important to see a doctor if any other symptoms are experienced.

Nipple hair can usually be easily treated and managed, should a woman choose to try to remove the hair for cosmetic reasons.

Adapted from https://www.medicalnewstoday.com/articles/320835.php

 

Patient’s Atypical Cushing’s Symptoms Lead to Discovery of Novel Genetic Mutations

New genetic mutations were found in a patient who exhibited atypical symptoms of Cushing’s syndrome, notably an abnormal protrusion of the eye, a case report shows.

The research, “Extensive ARMC5 genetic variance in primary bilateral macronodular adrenal hyperplasia that started with exophthalmos: a case report,” was published in the Journal of Medical Case Reports.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a disorder characterized by multiple lumps in the adrenal glands and excessive cortisol production. It is a rare cause of Cushing’s syndrome.

According to recent research, PBMAH is caused by mutations in the ARMC5 gene, which data suggest may act as a tumor suppressor.

Researchers presented the case of a 52-year-old Chinese woman who exhibited a protrusion of both eyes (exophtalmos), which was first thought to be Graves’ ophthalmopathy. An injection of triamcinolone acetonide, a corticosteroid, into the area behind the eye globe did not improve symptoms.

The patient later was diagnosed with diabetes, which was treated with insulin, and hypertension, treated with insulin and amlodipine. She also developed muscle weakness and bruised easily. She had no other relevant chronic illness or infectious disease, and did not smoke tobacco or drink alcohol.

Physical examination showed skin atrophy, moon face, buffalo hump (between the shoulders), and purplish abdominal striae (stretch marks), which researchers defined as a typical Cushingoid appearance. The patient also experienced elevated pressure inside the eye, and had edema, conjunctival congestion, and lid retraction. No liver, spleen, respiration, cardiac, abdominal, blood counts, urinary, sensory, or motor abnormalities were noted.

Biochemical evaluation showed elevated cortisol and reduced adrenocorticotropin (ACTH) levels. Administering  dexamethasone did not lower the level of cortisol. Abnormal responses of the hormone vasopressin also were detected.

A computed tomography (CT) scan of the adrenal glands showed bilateral multiple lobular masses, and an MRI of the eye orbits indicated bilateral exophthalmos with hypertrophy of the retro-orbital fat, which lines the orbit.

After PBMAH was diagnosed, the patient’s adrenal glands were removed. Pathological findings showed multiple, homogenous, golden-yellow-colored nodules on the glands.

The surgery successfully lowered the level of cortisol and increased that of ACTH. The patient began taking hydrocortisone and metformin for diabetes. After six months, her exophtlamos, blood glucose levels, and blood pressure had improved.

Genetic analysis revealed six specific ARMC5 mutations in five of the seven adrenal nodules analyzed. “All the mutations are novel and not found in available online databases,” the researchers wrote. The mutations may lead to resistance to cell death in the tumor cells, and cause an increase in the production of cortisol, they observed.

As a result of the ARMC5 mutations, gene expression (conversion of genetic information) of the messenger RNA (mRNA, which is converted from DNA in the first step of protein synthesis) was lower in the adrenal tumor samples, in comparison with normal adrenal cortex.

Overall, the study “highlights the importance of early recognition of atypical symptoms of Cushing’s syndrome such as exophthalmos, which would save the patient from harmful effects of excessive cortisol exposure,” the researchers said. Screening for ARMC5 mutations also would help improve diagnosis and genetic counseling, they said.

From https://cushingsdiseasenews.com/2018/02/13/odd-cushings-symptoms-linked-genetic-mutations-case-report/

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