A Large Benign Adrenocortical Adenoma Cosecreting Testosterone and Cortisol.

Most adrenal incidentalomas are benign neoplasms of the adrenal cortex. While the majority are nonfunctional, many secrete cortisol. Androgen- or estrogen-secreting adenomas are rare. A 44-year-old female, with history of hypertension and prediabetes, presented with worsening acne, hirsutism, secondary amenorrhea for 2 years, and a 40-pound weight gain. Laboratory evaluation showed high 24-hour urine free cortisol, suppressed adrenocorticotropic hormone (ACTH) level, indicative of ACTH independent Cushing syndrome, and elevated testosterone and androstenedione. Abdominal computed tomography (CT) revealed a 6.3 × 5.2 × 5.6 cm left adrenal mass. Patient underwent left open adrenalectomy. Pathology revealed benign adrenocortical adenoma. Postoperatively there was a significant improvement in her blood pressure and blood sugar levels, resumption of menses, and complete resolution of hyperandrogenism and hypercortisolism. We describe a patient with an adrenal adenoma cosecreting cortisol and androgen, leading to Cushing syndrome and significant virilization. Adrenal masses secreting androgens are less common and concerning for adrenocortical carcinoma (ACC). Patients with adrenal masses cosecreting multiple hormones should undergo workup expediently since ACC confers poor outcomes.

Histoplasmosis: An Unusual Cause of Adrenal Insufficiency.

OBJECTIVE: Adrenal insufficiency (AI), if not diagnosed in a timely manner, can lead to fatal outcomes. Here we describe an unusual case of AI secondary to disseminated histoplasmosis (DH) and the importance of being aware of the association of infections and AI. METHODS: A 56-year-old Hispanic man with untreated HIV infection presented for the evaluation of left upper jaw swelling and pain. A brain magnetic resonance imaging scan revealed a 4-cm soft-tissue mass in the left maxilla. Biopsy of the mass was consistent with histoplasmosis. He was also noted to have hyponatremia and hyperkalemia, which raised the suspicion of AI. Laboratory investigation showed a baseline cortisol level of 7 µg/dL (normal, 7-23 µg/dL) and adrenocorticotropic hormone level of 86 pg/mL (normal, 7-69 pg/mL). His 60-minute cortisol level after a 250-µg cosyntropin stimulation test was 9 µg/dL (normal, 7-23 µg/dL). Computed tomography of the chest incidentally noted bilateral adrenal enlargement. An adrenal biopsy was not pursued due to the high index of clinical suspicion of DH as the etiology of AI. RESULTS: He was diagnosed with adrenal histoplasmosis because of the evidence of AI and bilateral adrenal enlargement in the setting of DH. He was started on glucocorticoid replacement for primary AI and continues to be on glucocorticoids even after 5 years of diagnosis. DH frequently involves the adrenal gland (80%) and can present as adrenal enlargement but does not always cause primary AI. CONCLUSION: Our case demonstrates the importance of being vigilant about infections like histoplasmosis as a potential cause of AI. Delay in treatment in such cases could result in life-threatening consequences.

Empiric Determination of the Daily Glucocorticoid Replacement Dose in Adrenal Insufficiency.

BACKGROUND: For the treatment of adrenal insufficiency (AI) in adults, the Endocrine Society's recommended daily glucocorticoid replacement dose (DGRD) is 15 to 25 mg hydrocortisone (HC), which is approximately 1.7 times the reported mean daily cortisol production rate. Prolonged glucocorticoid overtreatment causes multiple morbidities. HYPOTHESIS: We tested the hypotheses that the DGRD, empirically determined by individual patient titration, is lower than that of the Endocrine Society guidelines and tolerated without evidence of glucocorticoid under-replacement. METHODS: We empirically determined the DGRD in 25 otherwise healthy adults with AI by titrating the DGRD to the lowest dose tolerated as judged by body mass index, blood pressure, serum sodium concentration and AI symptoms. Patients received either HC or prednisone (PRED). The HC equivalent of PRED was assumed to be 4:1. RESULTS: The mean empirically determined DGRD, expressed as HC equivalent, was significantly less than the midpoint of the Endocrine Society's recommended DGRD (7.6 ± 3.5 mg/m2 vs 11.8 mg/m2; P < 0.001). The DGRD in the adrenalectomy group was not significantly different than the DGRD of those with other AI causes (7.9 ± 4.0 mg/m2 vs 7.3 ± 3.1 mg/m2; P = ns), demonstrating that the empirically determined DGRD was not biased by residual cortisol secretion. There was no evidence of glucocorticoid under-replacement as determined by measured biometrics and AI symptoms. CONCLUSIONS: We conclude that an empirically determined DGRD is significantly lower than that of the Endocrine Society guidelines and tolerated without evidence of glucocorticoid under-replacement.

Thyroid Eye Disease due to Immune Reconstitution Inflammatory Syndrome as a Consequence of Antiretroviral Therapy in the Setting of AIDS.

We describe a case of worsening Graves' orbitopathy due to immune reconstitution inflammatory syndrome (IRIS) in a 38-year-old HIV-infected male after beginning ART (antiretroviral therapy). Two years after initiation of ART, the patient developed symptoms of hyperthyroidism and thyroid eye disease (TED) or Graves' orbitopathy (GO). Thyroid iodine uptake scan was consistent with Graves' disease. The CT scan of the orbits revealed minimal right-sided proptosis, consistent with GO. He was treated with methimazole and a short course of high-dose prednisone for GO. Thyroid function tests normalized, and eye symptoms eventually stabilized. This case demonstrates the importance of awareness and early recognition of IRIS in its many forms, as it has significant therapeutic implications.

A NOVEL MUTATION IN CALCIUM-SENSING RECEPTOR PRESENTING AS FAMILIAL HYPOCALCIURIC HYPERCALCEMIA IN A YOUNG MAN.

OBJECTIVE: Familial hypocalciuric hypercalcemia (FHH) is considered a relatively benign condition characterized by elevated serum calcium with relatively low urinary calcium excretion. It typically results from an altered set point in calcium homeostasis originating from mutations in the calcium-sensing receptor (CASR), AP2S1, or GNA11 genes, which encode for the calcium-sensing receptor (CaSR), adaptor-related protein complex 2, and G-protein alpha-11 subunit, respectively. Despite numerous reports of novel variants in these genes associated with FHH, new variants continue to be discovered. METHODS: We describe a 20-year-old man with a family history of hypercalcemia who had clinical findings compatible with FHH and no evidence of multiple endocrine neoplasia who underwent CASR gene sequencing for evaluation of hypercalcemia. Parathyroid gland single-photon emission computerized tomography scan was normal. RESULTS: CASR gene sequencing revealed a previously unreported heterozygous intronic variant at position 1608+3A>G (chromosome 3: 121994892) resulting in a 77-residue deletion. His mother has a history of bipolar disorder and hyperparathyroidism with an adenoma found on imaging, yet our patient had no evidence of adenoma and therefore no surgical intervention was recommended. Given that CaSR plays a role in parathyroid growth, some variants in CASR may ultimately lead to parathyroid hypertrophy and be mistaken for primary hyperparathyroidism. CONCLUSION: Long-term clinical follow up will be helpful in understanding the ultimate effects of specific CASR mutations on parathyroid growth or progression to significant hypercalcemia.

Effects of Parvovirus B19 Infection in Renal Transplant Recipients: A Retrospective Review of Three Cases.

Parvovirus B19 (PVB19) is a DNA virus which causes clinically relevant infection in renal transplant recipients (RTR) leading to significant morbidity. Manifestations include erythropoietin resistant anemia, proteinuria, and glomerulosclerosis in the allograft. Severe infection may require administration of intravenous immunoglobulin, reduction in immunosuppression and transfusions. The major challenge in managing and preventing the infection in RTR involves the act of balancing the decreased level of immunosuppression and the risk of rejection. The objective of this article is to understand the importance of PVB19 infection and its outcome in RTR. We reviewed the medical records of three RTR with confirmed PVB19 infection and recorded patient information including demographics, clinical and laboratory data, management, and outcome. The average time of occurrence of PVB19 infection as transplant was 8.6 weeks and they presented with symptomatic anemia. Elevated creatinine values were noted in two of them. Following treatment, anemia improved and creatinine values returned to baseline. One of them developed an early relapse and had to be treated once again similarly. We emphasize the importance of maintaining a high index of suspicion for PVB19 infection in patients with anemia in the posttransplant phase, especially in patients on higher doses of immunosuppressants. Early and proper treatment can prevent worsening clinical condition and possible effects on the allograft.