Hypopituitarism and COVID-19 – exploring a possible bidirectional relationship?

As of September 1, 2021, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus responsible for the coronavirus disease 2019 (COVID-19), has infected over 219 million and caused the deaths of over 4.5 million worldwide. Although COVID-19 has been traditionally associated with its ability to cause varied symptoms resembling acute respiratory distress syndrome (ARDS), emerging scientific evidence has demonstrated that SARS-CoV-2 causes much more damage beyond its effects on the upper respiratory tract.

To this end, in a recent study published in Reviews in Endocrine and Metabolic Disorders, the researchers discuss the extra-pulmonary manifestations of COVID-19.

Risk factors for severe COVID-19

It is now a well-known fact that the likelihood of people falling severely ill or dying from COVID-19 is increases if these individuals are obese, or have certain comorbidities like diabetes mellitus (DM), vitamin D deficiency, and vertebral fractures (VFs).

Any abnormality in the pituitary gland may lead to metabolic disorders, impaired immunity, and a host of other conditions that also make the body susceptible to infections. Since such conditions are common in patients with COVID-19 as well, it has been hypothesized that there might be a relationship between COVID-19 and pituitary gland disorders.

On the other hand, researchers have also observed that COVID-19 causes increased severity of pituitary-related disorders, and even pituitary apoplexy, which is a condition defined as internal bleeding or impaired blood supply in the pituitary gland. A group of Italian researchers has reviewed this bidirectional relationship between the pituitary gland abnormalities and COVID-19 in their study recently published in Reviews in Endocrine and Metabolic Disorders.

The link between pituitary gland abnormalities and COVID19

The pituitary gland releases hormones that regulate and control some of the most important functions of the body like growth, metabolism, energy levels, bone health, mood swings, vision, reproduction, and immunity, to name a few. The inability of the pituitary gland to release one or more of these hormones is known as ‘hypopituitarism.’  Factors responsible for hypopituitarism include traumatic brain injury, pituitary adenomas (tumors), genetic mutations, as well as infiltrative and infectious diseases.

Hypopituitarism can lead to severe cases of DM, growth hormone deficiency (GHD), abnormal lipid profile, obesity, arterial hypertension, and immune dysfunctions. Interestingly, similar consequences of COVID-19 have also been reported.

SARS-CoV-2 infects the human body by binding to a special class of receptors known as the angiotensin-converting enzyme 2 (ACE2) receptors. These receptors are located in the endothelial linings of most organs like the brain, heart, lungs, kidneys, intestine, liver, and pancreas, among others. The main function of the ACE2 receptors is binding to specific target molecules to maintain the renin-angiotensin system that is crucial for regulating dilation of blood vessels, as well as maintain blood glucose levels, the immune system, and homeostasis.

Therefore, SARS-CoV-2 binding to these ACE2 receptors facilitates the entry of this virus into all the organs that have these receptors, thus leading to the ability of SARS-CoV-2 to cause widespread damage in the body. Upon entry into the pancreas, for example, SARS-CoV-2 can inhibit ß-cells function, which worsens hyperglycemia and increases the risk for acute diabetic complications.

Similarly, the presence of ACE2 receptors in brain tissues may cause invasion into the pituitary gland and lead to pituitary apoplexy. The entry of SARS-CoV-2 into the brain can also cause neurological damage in infected patients, which may account for some of the common neurological complaints of COVID-19 including headaches, confusion, dysgeusia, anosmia, nausea, and vomiting.

Study findings

Hypopituitarism leading to metabolic syndrome has been scientifically linked to higher mortality in COVID-19 patients. In fact, the presence of a single metabolic syndrome component has been observed to double the risk of death by COVID-19. This risk was even higher among patients with DM and hypertension.

There was also an increased incidence of VFs in COVID-19 patients with hypopituitarism. Hence, patients with DM, obesity, hypertension, and chronic inflammatory disease, are all at an increased risk of poor outcomes and death in COVID-19.

Arterial hypertension is a common finding in adults with GHD, which is another consequence of hypopituitarism. Hypopituitarism also causes adrenal insufficiency, a condition that is primarily managed with glucocorticoids and hormonal replacement therapies.

Notably, patients with COVID-19 are often treated for prolonged periods with high-dose exogenous glucocorticoids, which is a class of steroids that suppress some activities of the immune system. This treatment approach may result in suppression of the hypothalamic-pituitary–adrenal axis that can lead to adrenal insufficiency.

Hypogonadism is another aspect of pituitary insufficiency that predisposes patients, especially males, to COVID-19. Evidence shows that males with hypogonadism were more frequently affected by metabolic syndrome.

Pituitary apoplexy, albeit rare, has also been linked to COVID-19, especially in patients with pituitary adenomas and those who are being treated with anticoagulant therapy. This may be because the pituitary gland becomes overstimulated during an infectious disease, which may increase pituitary blood demand and lead to sudden infarction precipitating acute apoplexy.

This phenomenon has also been shown in patients suffering from infectious diseases that cause hemorrhagic fevers. Taken together, pituitary apoplexy complicates treatment and management procedures in COVID-19 patients.

Despite the use of steroids in COVID-19 patients, there have been no contraindications for vaccination in such patients. However, those on extensive hormonal therapies need constant monitoring for best results.

Implications

The pituitary gland acts like a double-edged sword for COVID-19. On one end, hypopituitarism predisposes patients to metabolic disorders like DM, obesity, and VFs, all of which are known risk factors for COVID-19.

On the other hand, COVID-19 may cause direct or indirect damage to the pituitary glands by entering the brain and inducing unfavorable vascular events – though evidence on this remains lesser in comparison to that of hypopituitarism. Ultimately, the researchers of the current study conclude that managing patients with hormonal insufficiencies optimally with steroids is likely to improve outcomes in severe COVID-19.

Journal reference:

Primary Adrenal Insufficiency Due to Bilateral Adrenal Infarction in COVID-19

This article was originally published here

J Clin Endocrinol Metab. 2021 Jul 29:dgab557. doi: 10.1210/clinem/dgab557. Online ahead of print.

ABSTRACT

CONTEXT: Coronavirus disease 2019 (COVID-19) is a proinflammatory and prothrombotic condition, but its impact on adrenal function has not been adequately evaluated.

CASE REPORT: A 46-year-old woman presented with abdominal pain, hypotension, and skin hyperpigmentation after COVID-19 infection. The patient had hyponatremia, serum cortisol <1.0 µg/dL, adrenocorticotropin (ACTH) of 807 pg/mL, and aldosterone ❤ ng/dL. Computed tomography (CT) findings of adrenal enlargement with no parenchymal and minimal peripheral capsular enhancement after contrast were consistent with bilateral adrenal infarction. The patient had autoimmune hepatitis and positive antiphospholipid antibodies, but no previous thrombotic events. The patient was treated with intravenous hydrocortisone, followed by oral hydrocortisone and fludrocortisone.

DISCUSSION: We identified 9 articles, including case reports, of new-onset adrenal insufficiency and/or adrenal hemorrhage/infarction on CT in COVID-19. Adrenal insufficiency was hormonally diagnosed in 5 cases, but ACTH levels were measured in only 3 cases (high in 1 case and normal/low in other 2 cases). Bilateral adrenal nonhemorrhagic or hemorrhagic infarction was identified in 5 reports (2 had adrenal insufficiency, 2 had normal cortisol levels, and 1 case had no data). Interestingly, the only case with well-characterized new-onset acute primary adrenal insufficiency after COVID-19 had a previous diagnosis of antiphospholipid syndrome. In our case, antiphospholipid syndrome diagnosis was established only after the adrenal infarction triggered by COVID-19.

CONCLUSION: Our findings support the association between bilateral adrenal infarction and antiphospholipid syndrome triggered by COVID-19. Therefore, patients with positive antiphospholipid antibodies should be closely monitored for symptoms or signs of acute adrenal insufficiency during COVID-19.

PMID:34463766 | DOI:10.1210/clinem/dgab557

Estrogen receptor α plays an important role in Cushing’s syndrome during pregnancy

Abstract

Cushing’s syndrome (CS) during pregnancy is very rare with a few cases reported in the literature.

Of great interest, some cases of CS during pregnancy spontaneously resolve after delivery. Most studies suggest that aberrant luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (LHCGR) seems to play a critical role in the pathogenesis of CS during pregnancy.

However, not all women during pregnancy are observed cortisol hypersecretion. Moreover, some cases of adrenal tumors or macronodular hyperplasia with LHCGR expressed, have no response to hCG or LH.

Therefore, alternative pathogenic mechanisms are indicated. It has been recently reported that estrogen binding to estrogen receptor α (ERα) could enhance the adrenocortical adenocarcinoma (ACC) cell proliferation.

Herein, we hypothesize that ERα is probably involved in CS development during pregnancy.

Better understanding of the possible mechanism of ERα on cortisol production and adrenocortical tumorigenesis will contribute to the diagnosis and treatment of CS during pregnancy.

Read the entire article here: https://www.sciencedirect.com/science/article/pii/S0306987720303893?via%3Dihub

(For the General Public) Are there any advantages to human growth hormone?

Harvard Men’s Health Watch

Ask the doctor

Q. I’ve heard about the benefits of human growth hormone (HGH) for older individuals. Is this something I should try?

A. The benefits of HGH supplementation for older adults are unproven, and perhaps most telling is that these products have a negligible effect on HGH levels. In addition, there are concerns about potential side effects.

HGH comes in two forms: injections and pills. Since HGH injections are difficult to administer, pills are often preferred. Yet, these supplements do not actually contain HGH like injections do, because the hormone would quickly break down in the digestive tract. Instead, they contain amino acids that are absorbed by the body, which raises HGH levels. (They are also more expensive and can cost $100-plus for a month’s supply.)

HGH levels naturally decline as people age, which makes sense since our bodies stop growing during the late teenage years. So why would you need higher HGH levels later in life? The hype around HGH comes from a few studies that showed HGH injections can increase lean body mass and shrink body fat, which led to claims of HGH as an “anti-aging” hormone. However, the effects on strength and body weight are quite minimal. In addition, HGH can increase the amount of soft tissues in the body, which can lead to swelling, joint pain, carpal tunnel syndrome, and breast tenderness in men.

There is also a concern that HGH might promote cancer growth. (MaryO’Note:  I always mentioned this to doctors when I was diagnosed with kidney cancer.  Even though I couldn’t take HGH for the first 5 years after diagnosis, none of my doctors would confirm a connection between HGH and my cancer)

If you want to improve your strength, forget about HGH and increase your exercise. Some studies suggest this alone may be more effective than HGH supplementation for raising growth hormone levels in the body.

—William Kormos, MD
Editor in Chief, Harvard Men’s Health Watch

Originally published: July 2016

Adapted from http://www.health.harvard.edu/mens-health/are-there-any-advantages-to-human-growth-hormone

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