Background Hyperandrogenism presenting during pregnancy usually arises due to pregnancy-related conditions, as pre-existing high androgen levels typically lead to anovulation and infertility (1) . These conditions are rare and can occur at
Gautam Das, Vinay S Eligar, Jyothish Govindan and D Aled Rees
Priya Vaidyanathan and Paul Kaplowitz
(ng/dL) 1660 <1000 Free testosterone (pg/dL) 344.6 18–111 Estradiol (pg/mL) 64 <54 Estrone (pg/mL) 51 15–65 Karyotype 46,XY Investigation Partial androgen insensitivity syndrome (PAIS) was
Chrisanthi Marakaki, Anna Papadopoulou, Olga Karapanou, Dimitrios T Papadimitriou, Kleanthis Kleanthous and Anastasios Papadimitriou
wasting 21-OHD accounts for approximately 75% of the patients presenting with both signs of androgen excess and symptoms of mineralocorticoid deficiency, the latter being absent in the remaining 25% presenting the simple virilizing type. Non-classical CAH
Ravi Kumar Menon, Francesco Ferrau, Tom R Kurzawinski, Gill Rumsby, Alexander Freeman, Zahir Amin, Márta Korbonits and Teng-Teng L L Chung
not have symptoms or signs suggestive of phaeochromocytoma, glucocorticoid or androgen excess. She had multiple cutaneous neurofibromas, café-au-lait spots, axillary freckling, kyphoscoliosis, and severe myopia. She also had a multi-nodular goitre
M A Shehab, Tahseen Mahmood, M A Hasanat, Md Fariduddin, Nazmul Ahsan, Mohammad Shahnoor Hossain, Md Shahdat Hossain and Sharmin Jahan
causing androgen excess, and the latter androgen deficiency and thus displaying a distinctive pattern of amalgamation, defying the popular notion of Occam’s razor. Case presentation A 7-year-old child was referred to us from the department of
Jayshree Swain, Shruti Sharma, Ved Prakash, N K Agrawal and S K Singh
infrequently, granulosa–theca tumor. Nonfunctional ovarian neoplasms such as epithelial cystadenomas or cystadenocarcinomas may rarely present with androgen excess by stimulating steroidogenesis in the adjacent nonneoplastic ovarian stroma. Our patient
Diana Oliveira, Mara Ventura, Miguel Melo, Sandra Paiva and Francisco Carrilho
ACTH: 138 pg/mL (RR: 9–52), leading to diagnostic confirmation. Aldosterone and adrenal androgens levels were low; anti-21-hydroxylase antibodies were negative; thyroid function was normal and there were no anterior pituitary deficits ( Table 1
Casey M Hay and Daniel I Spratt
A 55-year-old woman with asthma presented with adrenal insufficiency of unknown origin. She was referred to our Division of Reproductive Endocrinology to further evaluate an undetectable morning cortisol level discovered during the evaluation of a low serum DHEA-S level. She was asymptomatic other than having mild fatigue and weight gain. Her medication list included 220 μg of inhaled fluticasone propionate twice daily for asthma, which she was taking as prescribed. On presentation, the undetectable morning cortisol level was confirmed. A urinary measurement of fluticasone propionate 17β-carboxylic acid was markedly elevated. Fluticasone therapy was discontinued and salmeterol therapy initiated with supplemental hydrocortisone. Hydrocortisone therapy was discontinued after 2 months. A repeat urinary fluticasone measurement 4 months after the discontinuation of fluticasone therapy was undetectably low and morning cortisol level was normal at 18.0 μg/dl. Inhaled fluticasone is generally considered to be minimally systemically absorbed. This patient's only clinical evidence suggesting adrenal insufficiency was fatigue accompanying a low serum DHEA-S level. This case demonstrates that adrenal insufficiency can be caused by a routine dose of inhaled fluticasone. Missing this diagnosis could potentially result in adrenal crisis upon discontinuation of fluticasone therapy.
- Standard-dose inhaled fluticasone can cause adrenal insufficiency.
- Adrenal insufficiency should be considered in patients taking, or who have recently discontinued, inhaled fluticasone therapy and present with new onset of nonspecific symptoms such as fatigue, weakness, depression, myalgia, arthralgia, unexplained weight loss, and nausea that are suggestive of adrenal insufficiency.
- Adrenal insufficiency should be considered in postoperative patients who exhibit signs of hypoadrenalism after fluticasone therapy has been withheld in the perioperative setting.
- Routine screening for hypoadrenalism in patients without clinical signs or symptoms of adrenal insufficiency after the discontinuation of inhaled fluticasone therapy is not indicated due to the apparently low incidence of adrenal insufficiency caused by fluticasone.
Jasmeet Kaur, Alan M Rice, Elizabeth O’Connor, Anil Piya, Bradley Buckler and Himangshu S Bose
Congenital adrenal hyperplasia (CAH) is caused by mutations in cytochrome P450 side chain cleavage enzyme (CYP11A1 and old name, SCC). Errors in cholesterol side chain cleavage by the mitochondrial resident CYP11A1 results in an inadequate amount of pregnenolone production. This study was performed to evaluate the cause of salt-losing crisis and possible adrenal failure in a pediatric patient whose mother had a history of two previous stillbirths and loss of another baby within a week of birth. CAH can appear in any population in any region of the world. The study was conducted at Memorial University Medical Center and Mercer University School of Medicine. The patient was admitted to Pediatric Endocrinology Clinic due to salt-losing crisis and possible adrenal failure. The patient had CAH, an autosomal recessive disease, due to a novel mutation in exon 5 of the CYP11A1 gene, which generated a truncated protein of 286 amino acids compared with wild-type protein that has 521 amino acids (W286X). Although unrelated, both parents are carriers. Mitochondrial protein import analysis of the mutant CYP11A1 in steroidogenic MA-10 cells showed that the protein is imported in a similar fashion as observed for the wild-type protein and was cleaved to a shorter fragment. However, mutant’s activity was 10% of that obtained for the wild-type protein in non-steroidogenic COS-1 cells. In a patient of Mexican descent, a homozygous CYP11A1 mutation caused CAH, suggesting that this disease is not geographically restricted even in a homogeneous population.
- Novel mutation in CYP11A1 causes CAH;
- This is a pure population from Central Mexico;
- Novel mutation created early truncated protein.
Catarina Roque, Ricardo Fonseca, Carlos Tavares Bello, Carlos Vasconcelos, António Galzerano and Sância Ramos
Primary adrenal lymphoma is a rare malignancy. It frequently presents bilaterally and with symptoms of adrenal insufficiency. Amiodarone may induce secondary organ dysfunction, and thyrotoxicosis develops in 15% of cases. The symptomatology of both conditions is nonspecific, especially in the elderly, and a high suspicion index is necessary for appropriate diagnosis. A 78-year-old female presented to the emergency department with confusion, nausea and vomiting. She had recently been to the emergency department with urinary tract infection, vomiting and acute hypochloremic hyponatremia. Upon re-evaluation, the leukocyturia persisted and because of TSH 0.01 µU/mL and free-T4 68 (10–18) pmol/L, she was admitted to the Endocrinology ward. Further evaluation supported amiodarone-induced thyroiditis type 2. Sepsis ensued, in the setting of nosocomial pneumonia. Hemodynamic instability, hyponatremia, hypoglycemia and vomiting raised the suspicion of adrenocortical insufficiency. Fluid resuscitation and hydrocortisone led to clinical improvement, and adrenal insufficiency was admitted. The thoracoabdominal tomography suggested an endobronchic primary lesion with hepatic and adrenal secondary deposits (6.6 and 7 cm), but this was confirmed neither on pleural effusion nor on bronchofibroscopic fluid analyses. The adrenals were not accessible for biopsy. Despite high-dose hydrocortisone maintenance, the patient died before definite diagnosis. The autopsy confirmed primary non-Hodgkin lymphoma.
- Primary adrenal lymphoma is a rare cause of adrenal insufficiency, but progression can be fast and fatal.
- Hyperpigmentation is frequently absent.
- The presenting symptoms are nonspecific and might mimic infection. Disproportion of the general state with signs of specific organ symptomatology is a diagnostic clue.
- Infection may precipitate adrenal crisis and worsen thyroid function with further adrenal insufficiency exacerbation.
- In the context of thyrotoxicosis, there may be little clinical response to a therapeutic trial with standard dose glucocorticoids.
- High-dose glucocorticoid substitution may be required to achieve clinical stability in thyrotoxic patients.