Summary

Acute illness-related stress can result in severe hypercortisolism and bilateral adrenal enlargement in certain patients. We report a case of stress-induced hypercortisolism and bilateral adrenal enlargement in a patient admitted for acute respiratory distress and cardiogenic shock. Bilateral adrenal enlargement and hypercortisolism found during hospitalization for acute illness resolved 3 weeks later following the resolution of acute illness. Acute illness can be a precipitating factor for stress-induced hypercortisolism and bilateral adrenal enlargement. We hypothesize that increased adrenocorticotrophic hormone mediated by corticotrophin-releasing hormone from physical stress resulted in significant adrenal hyperplasia and hypercortisolism. This mechanism is downregulated once acute illness resolves.

Learning points

• Adrenal enlargement with abnormal adrenal function after stress is uncommon in humans; however, if present, it can have self-resolution after the acute illness is resolved.

• Stress induces enlargement of the adrenals, and the degree of cortisol elevation could be very massive. This process is acute, and the absence of cushingoid features is expected.

• Treatment efforts should be focused on treating the underlying condition.

Summary

Painful peripheral polyneuropathy is a common complication of diabetes mellitus (DM) and is a significant source of chronic disability and remains a challenging condition with no available disease-modifying treatment. In the present case report, we describe the treatment of a patient featuring painful diabetic neuropathy with perineural injections of autologous plasma rich in growth factors (PRGF). At one-year post-procedure, the patient exhibited improved scores on the neuropathic pain scale and improvement in the activity level.

Learning points

• Plasma rich in growth factors (PRGF) is an autologous product that can be prepared and administered in a physician’s office.

• PRGF can be infiltrated as a liquid, creating a three-dimensional gel scaffold in the body.

• PRGF releases growth factors involved in nerve healing.

• PRGF may be established as a potent alternative treatment of painful diabetic polyneuropathy.

Summary

We present the first report of use of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) in a hypoparathyroid patient during early pregnancy and lactation. The patient developed postoperative hypoparathyroidism as a 28-year-old woman following total thyroidectomy for multinodular goiter. She was not well controlled with conventional therapy, and started rhPTH(1-84) in 2015 following its approval in the United States. She became pregnant in 2018 at age 40. She discontinued rhPTH(1-84) therapy at 5 weeks gestation but resumed in the postpartum period while breastfeeding. Her daughter’s serum calcium was borderline elevated at 8 days postpartum but within the normal range at 8 weeks postpartum. The patient stopped nursing at around 6 months postpartum. Her daughter is now at 4 years and 5 months of age and is healthy and meeting developmental milestones. She was again pregnant at 8 months postpartum from her first pregnancy, and she made an informed decision to continue parathyroid hormone. At 15 weeks gestation, rhPTH(1-84) was recalled in the United States due to issues with the delivery device, and she discontinued rhPTH(1-84) treatment and resumed calcium and calcitriol supplements. She gave birth to a baby boy at 39 weeks in January 2020. At 3 years and 2 months of age, he is overall healthy. Further data are needed regarding the safety of rhPTH(1-84) in pregnancy and lactation.

Learning points

• rhPTH(1-84) is approved for therapy of patients with hypoparathyroidism; however, there are no data regarding the safety of treatment during nursing and pregnancy.

• There are multiple alterations in mineral metabolism during normal pregnancy and lactation.

Summary

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism triggered by precipitants that increase the activity of the sodium-potassium pump in the skeletal muscle. In our case study, a previously healthy 34-year-old male presented to the emergency department with new onset thyrotoxicosis, secondary to Graves’ disease. Given the severity of his triiodothyronine (T3) thyrotoxicosis, he was admitted and started on a high dose of beta-blocker, thioamides, and intravenous hydrocortisone. On the second day of his hospitalization, he developed acute flaccid paralysis of his lower extremities. Subsequent stroke workup was negative, and his electrolytes revealed severe hypokalemia and hyperglycemia consistent with TPP. He was treated with potassium and had a complete recovery of his paralysis and hypokalemia within hours. The patient has not had any recurrence since this singular episode in the hospital. This case highlights the scenario where the treatment of hyperthyroidism with high-dose corticosteroids to reduce the conversion of thyroxine to T3 inadvertently resulted in TPP. Clinicians should be aware of this potentially rare but serious consequence of using steroids to manage hyperthyroidism.

Learning points

• High-dose steroids used to treat hyperthyroidism in hospitalized patients may rarely precipitate thyrotoxic periodic paralysis (TPP) by inducing hypokalemia and hyperglycemia.

• TPP should be included in the differential diagnosis for acute flaccid paralysis in hospitalized patients with hyperthyroidism.

• Since TPP is associated with trans-cellular shifts in potassium instead of total body potassium depletion, conservative repletion of potassium is recommended to avoid rebound hyperkalemia.

Summary

Depot medroxyprogesterone acetate, also known as Depo-Provera, is a progesterone-only contraceptive that is administered by injection to patients every three months. We describe the case of a 19-year-old female who was diagnosed with central diabetes insipidus following the administration of the contraceptive injection Depo-Provera. The patient was diagnosed with polycystic ovarian syndrome at age 16 and was originally prescribed oral contraceptives to restore menstrual regularity. Three years later, Depo-Provera was substituted for convenience, and symptoms of polyuria and polydipsia appeared one month after initiating the progesterone-only regimen. We are proposing that central diabetes insipidus may be a possible adverse effect of Depo-Provera in women with polycystic ovarian syndrome who receive the progesterone-only contraception, due to the interference of their arginine vasopressin mechanism through the alteration of estrogen levels. We review potential mechanisms through the presentation of previously completed research in polycystic ovarian syndrome.

Learning points

• We propose that although rare, the decrease in estrogen that is experienced during the administration of Depo-Provera can interfere with arginine vasopressin release in patients with polycystic ovarian syndrome (PCOS).

• Increased awareness of possible lasting adverse effects on fluid balance with unopposed progesterone administration in PCOS is important, as this case of the development of diabetes insipidus suggests.

• Discussion of such potential side effects is important when considering contraceptive options for the regulation of menses in patients with PCOS.

Summary

Adult-onset nesidioblastosis is a rare complication of Roux-en-Y gastric bypass surgery and may occur months to years after the initial surgical procedure. It is manifested by a hyperinsulinemic, hypoglycemic state. The annual incidence of adult-onset hyperinsulinemic hypoglycemia is believed to be less than 0.1 in 1 000 000 with a mean age of onset of 47 years (1). Here, we describe a patient who presented with worsening hypoglycemic symptoms for 1 year prior to presentation that eventually progressed to hypoglycemic seizures. The onset of this hypoglycemia was 5 years after Roux-en-Y gastric bypass surgery. A full neurological evaluation, which included an EEG, head CT, and MRI, was performed to rule out epilepsy and other seizure-related disorders. After hypoglycemia was confirmed, extensive laboratory studies were obtained to elucidate the cause of the hypoglycemia and differentiate nesidioblastosis from insulinoma. Once the diagnosis of nesidioblastosis was established, a sub-total pancreatectomy was performed, and the patient was discharged and placed on acarbose, a competitive reversible inhibitor of pancreatic α-amylase and intestinal brush border α-glucosidases which slows carbohydrate absorption. The lack of information and understanding of nesidioblastosis due to its rarity makes any knowledge of this rare but important surgical complication essential. As incidence of obesity increases, the number of gastric bypasses being performed increases with it, and understanding this disease process will be essential for the primary care provider. This is the primary reason for the writing of this publication.

Learning points

• Nesidioblastosis is a persistent hyperinsulinemic, hypoglycemic state, mostly seen after Roux-en-Y gastric bypass surgery, with symptoms occurring postprandially.

• The incidence is 0.1–0.3% of all post Roux-en-Y gastric bypass patients.

• The key diagnostic clue to identifying nesidioblastosis is a positive selective arterial calcium stimulation test, showing a diffuse pattern of increased basal hepatic venous insulin concentration, whereas insulinomas would show focal increases.

• Pathological specimen of pancreas will show diffuse hypertrophy of beta cells.

• Management includes acarbose and total or subtotal pancreatectomy, which can be curative.

• With the prevalence of obesity increasing and more patients turning to Roux-en-Y gastric bypass, more patients may be at risk of this potential surgical complication.

Summary

Tumor-induced osteomalacia (TIO) is a rare form of osteomalacia caused by fibroblast growth factor-23 (FGF23)-secreting tumors. Most of these tumors are phosphaturic mesenchymal tumors (PMTs) typically involving soft tissue in the extremities and bone of the appendicular skeleton and cranium. We report the case of a 60-year-old woman with about 3 years of persistent bone pain and multiple fractures, initially diagnosed as osteoporosis, who was found to have hypophosphatemia with low 1,25-dihydroxyvitamin D and elevated alkaline phosphatase and inappropriately normal FGF23 consistent with TIO. Her symptoms improved with phosphate supplementation, vitamin D and calcitriol. ⁶⁸Ga-DOTATATE imaging revealed a T12 vertebral body lesion confirmed on biopsy to be a PMT. She underwent resection of the PMT with resolution of TIO and increased bone density. This rare case of TIO secondary to a PMT of the thoracic spine highlights some of the common features of PMT-associated TIO and draws attention to PMT-associated TIO as a possible cause of unexplained persistent bone pain, a disease entity that often goes undiagnosed and untreated for years.

Learning points

• Tumor-induced osteomalacia (TIO) is typically caused by phosphaturic mesenchymal tumors (PMTs) that are usually found in the soft tissue of the extremities and bone of the appendicular skeleton/cranium and rarely in the spine.

• TIO may be misdiagnosed as osteoporosis or spondyloarthritis, and the correct diagnosis is often delayed for years. However, osteoporosis, in the absence of fracture, is not associated with bone pain.

• The hallmark of TIO is hypophosphatemia with inappropriately normal or low 1,25-dihydroxyvitamin D and elevated or inappropriately normal fibroblast growth factor-23 (FGF23) levels.

• In patients with unexplained persistent bone pain, a serum phosphate should be measured. Consider PMT-associated TIO as a potential cause of unexplained persistent bone pain and hypophosphatemia.

• PMTs express somatostatin receptors and may be identified with ⁶⁸Ga-DOTATATE imaging.

• Complete surgical resection is the preferred treatment for spinal PMTs associated with TIO.

Summary

A 52-year-old female presented with recurrent episodes of fasting or post-absorptive hypoglycemia. A 72-h fasting test confirmed endogenous hyperinsulinemia. Conventional imaging was unremarkable. Selective pancreatic arterial calcium stimulation and hepatic venous sampling showed a maximum calcium-stimulated insulin concentration from several pancreatic areas, mainly the proximal splenic artery and the proximal gastroduodenal artery, suggesting the presence of one or more occult insulinoma(s) in the region of the pancreatic body. ⁶⁸Ga-DOTA-exendin-4 PET/CT showed however generalized increased uptake in the pancreas and a diagnosis of nesidioblastosis was therefore suspected. The patient has been since successfully treated with dietetic measures and diazoxide. Treatment efficacy was confirmed by a flash glucose monitoring system with a follow-up of 7 months.

Learning points

• Adult nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia.

• The distinction between insulinoma and nesidioblastosis is essential since the therapeutic strategies are different.

• ⁶⁸Ga-DOTA-exendin-4 PET/CT emerges as a new noninvasive diagnostic tool for the localization of an endogenous source of hyperinsulinemic hypoglycemia.

• Medical management with dietetic measures and diazoxide need to be considered as a valuable option to treat patients with adult nesidioblastosis.

• Flash glucose monitoring system is helpful for the evaluation of treatment efficacy.

Summary

We describe a case of a 47-year-old patient who presented with severe lactic acidosis, troponinemia, and acute kidney injury after receiving 8 mg of intramuscular dexamethasone for seasonal allergies in the setting of an undiagnosed epinephrine-secreting pheochromocytoma. This case was atypical, however, in that the patient exhibited only mildly elevated noninvasive measured blood pressures. Following a period of alpha-adrenergic blockade, the tumor was resected successfully. Steroid administration can precipitate pheochromocytoma crisis that may present unusually as in our patient with mild hypertension but profound lactic acidosis.

Learning points

• Steroids administered via any route can precipitate pheochromocytoma crisis, manifested by excessive catecholamine secretion and associated sequelae from vasoconstriction.

• Lack of moderate/severe hypertension on presentation detracts from consideration of pheochromocytoma as a diagnosis.

• Lactatemia after steroid administration should prompt work-up for pheochromocytoma, as it can be seen in epinephrine-secreting tumors.

• Noninvasive blood pressure measurements may be unreliable during pheochromocytoma crisis due to excessive peripheral vasoconstriction.

Summary

Diabetes mellitus type 2 (DM-2) is one of the important causes of low-grade chronic inflammation (meta inflammation) seen in almost all tissues in the body. Other possible mechanisms involved in the development of lower urinary tract symptoms (LUTS) with DM-2 are the hypertonicity of the peripheral sympathetic nerves and hyperinsulinemia effects on the autonomous nervous system activity. These further suggests that abnormalities in glucose homeostasis influence the hyperproliferation of the prostate cells resulting in benign prostatic hyperplasia (BPH). Similarly, hepatic steatosis, a form of non-alcoholic fatty liver disease (NAFLD) prevalence among patients with DM-2, is as high as 75%. NAFLD has no symptoms in most diabetic patients. In this study, we present a case of a 64-year-old Black male who had worsening urinary urgency and hesitancy for 4 months, with increasing abdominal girth. Patient was found to have symptoms, diagnostic studies, and physical exam findings indicative of BPH and fatty liver disease. He was treated with hepato-protective medications, tighter control of his blood glucose levels, and blood pressure meds for 13 months. Upon follow-up, most of his symptoms were resolved. Timeline of BPH resolution and decrease in liver size following treatment suggest that DM-2 has a strong correlation with the development of BPH and fatty liver disease in most patients living with diabetes.

Learning points

• Men with type 2 diabetes mellitus (DM-2) tend to have significantly lower serum PSA level, lower testosterone levels, and larger prostate volume compared to non-diabetic male patients.

• Patients with DM-2 have higher prevalence of hepatic steatosis, liver cirrhosis, and end-stage liver failure.

• The role of metformin in reducing hepatic steatosis as stated by several studies is yet to be validated as our patient has been on metformin for 22 years for the management of DM-2 with fatty liver disease.