Clinical Overview > Gland/Organ

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Taieb Ach Department of Endocrinology and Diabetology, Douai Hospital Center, Douai, France
Department of Endocrinology, University Hospital of Farhat Hached Sousse

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Perrine Wojewoda Department of Endocrinology and Diabetology, Douai Hospital Center, Douai, France

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Flora Toullet Department of Endocrinology and Diabetology, Douai Hospital Center, Douai, France

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Roxane Ducloux Department of Endocrinology and Diabetology, Douai Hospital Center, Douai, France

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Véronique Avérous Department of Endocrinology and Diabetology, Douai Hospital Center, Douai, France

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Summary

Multiple endocrine metastases are a rare but possible complication of lung adenocarcinoma (LAC). Pituitary metastasis is a rare condition with poor clinical expression. Diabetes insipidus (DI) is its most common presenting symptom. Here we report an original case of a pituitary stalk (PS) metastasis from LAC presenting as central DI followed by adrenal insufficiency (AI) from bilateral adrenal metastasis, without known evidence of the primary malignancy. A 45-year-old woman whose first clinical manifestations were polyuria and polydipsia was admitted. She was completely asymptomatic with no cough, no weight loss or anorexia. Chest radiography was normal. Brain MRI showed a thick pituitary stalk (PS). DI was confirmed by water restriction test and treated with vasopressin with great clinical results. Explorations for systemic and infectious disease were negative. Few months later, an acute AI led to discovering bilateral adrenal mass on abdominal CT. A suspicious 2.3 cm apical lung nodule was found later. Histopathological adrenal biopsy revealed an LAC. The patient received systemic chemotherapy with hormonal replacement for endocrinological failures by both vasopressin and hydrocortisone. We present this rare case of metastatic PS thickness arising from LAC associated with bilateral adrenal metastasis. Screening of patients with DI and stalk thickness for lung and breast cancer must be considered. Multiple endocrine failures as a diagnostic motive of LAC is a rare but possible circumstance.

Learning points:

  • Adrenal metastasis is a common location in lung adenocarcinoma; however, metastatic involvement of the pituitary stalk remains a rare occurrence, especially as a leading presentation to diagnose lung cancer.

  • The posterior pituitary and the infundibulum are the preferential sites for metastases, as they receive direct arterial blood supply from hypophyseal arteries.

  • Patients diagnosed with diabetes insipidus due to pituitary stalk thickness should be considered as a metastasis, after exclusion of the classical systemic and infectious diseases.

  • The diagnosis of an endocrinological metastatic primary lung adenocarcinoma for patients without respiratory symptoms is often delayed due to a lack of correlation between endocrinological symptoms and lung cancer.

  • The main originality of our case is the concomitant diagnosis of both endocrinological failures, as it was initiated with a diabetes insipidus and followed by an acute adrenal insufficiency.

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Gueorgui Dubrocq Divisions of Infectious Diseases

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Andrea Estrada Divisions of Endocrinology and Diabetes

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Shannon Kelly Divisions of Orthopaedic Surgery, Department of Pediatrics, Children’s National Medical Center, Washington, District of Columbia, USA

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Natella Rakhmanina Divisions of Infectious Diseases
Elizabeth Glaser Pediatric AIDS Foundation, Washington, District of Columbia, USA

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Summary

An 11-year-old male with perinatally acquired human immune deficiency virus (HIV) infection on antiretroviral regimen, which included abacavir plus lamivudine (Epzicom), didanosine, ritonavir and atazanavir presented with bilateral axillary striae, increased appetite, fatigue, facial swelling and acute weight gain. Two months prior to presentation, the patient had received a diagnostic and therapeutic intra-articular triamcinolone injection in the knee for pain relief and subsequently became progressively swollen in the face, developed striae bilaterally at the axillae, experienced increased appetite, fatigue and an 8 pound weight gain. During the endocrine workup, suspicion for adrenal insufficiency prompted 24-h urine collection for free cortisol, which was found to be undetectable (below LLQ of 1.0 µg/L). This prompted further evaluation of the hypothalamic–pituitary axis (HPA) by standard dose adrenocorticotropic hormone (ACTH) stimulation test. A 250 µg cosyntropin stimulation test was performed and confirmed HPA axis suppression. Baseline cortisol level was <1 µg/dL and stimulated cortisol level at 30 min was 3.8 µg/dL. The patient was diagnosed with iatrogenic Cushing syndrome and suppression of HPA axis secondary to the drug interaction between ritonavir (RTV) and intra-articular triamcinolone injection. Following endocrine evaluation and workup, the patient was admitted for planned orthopaedic procedure including elective left hamstring lengthening, distal femoral osteotomy and patellar tendon advancement. Taking into consideration the diagnosis of iatrogenic Cushing syndrome, at the start of the surgical procedure, 100 mg IV stress dose of hydrocortisone followed by 50 mg hydrocortisone every 8 h for 24 h was administered. Stress dosing was discontinued 24 h after the procedure. Throughout the hospitalization and upon discharge, the patient continued his ART. From initial presentation, patient has remained clinically stable throughout surgery and postoperative period.

Learning points:

  • Drug–drug interaction between ritonavir and triamcinolone can cause Cushing syndrome.

  • Although triamcinolone has a half-life of 3 h, an intra-articular injection may be systematically absorbed for 3 weeks after injection, and adrenal suppression may last as long as 30 days.

  • Co-administration of ritonavir and corticosteroids may result in an increase of plasma levels of corticosteroids levels, as they are both eliminated by CYP3A metabolism, and this interaction has the potential to prolong the half-life of triamcinolone several fold.

  • No specific guidelines are available for the management of iatrogenic Cushing syndrome secondary to ritonavir and corticosteroids.

  • One treatment option includes replacing ritonavir with a non-protease inhibitor-based regimen.

  • Initiating hydrocortisone replacement therapy to prevent an adrenal crisis is also an alternate option.

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Siew Hui Foo
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Shahada A H Sobah Department of Haematology, Ampang Hospital, Selangor, Malaysia

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Summary

Hypopituitarism is a rare presentation of Burkitt's lymphoma (BL). The purpose of this report is to present a case of BL presenting with panhypopituitarism and to review other case reports of lymphoma presenting with pituitary dysfunction to highlight the distinguishing features of these cases from other benign aetiologies of pituitary dysfunction such as non-functioning pituitary adenomas. We reviewed a total of 11 cases of lymphoma presenting with pituitary dysfunction published from 1998 to 2013 including the present case. The demographics, clinical presentations, laboratory features, radiological findings, histological diagnosis, treatment administered and outcomes were described. Of the total number of patients, 45.5% of the cases had diffuse large B-cell lymphoma while 27.3% had BL. Anterior pituitary dysfunction was more common than posterior pituitary dysfunction at presentation. The other common associated presenting symptoms were painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms. Hypothalamic–pituitary abnormalities were often demonstrated radiologically to be associated with cavernous sinus and/or stalk involvement. All patients who completed immunochemotherapy responded haematologically. Pituitary dysfunction also improved in most cases although the recovery tended to be partial. In conclusion, a high index of suspicion of underlying malignancy, such as lymphoma, should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, rapidly evolving neurological features, radiological features atypical of a pituitary adenoma and constitutional symptoms. An early diagnosis is essential as prompt initiation of definitive therapy will induce disease remission and recovery of pituitary dysfunction.

Learning points

  • Hypopituitarism may be the presenting symptom of lymphoma in the absence of associated overt symptoms or signs of a haematological malignancy resulting in delay in diagnosis and institution of treatment.

  • Pituitary dysfunction due to tumour infiltration has a greater tendency to involve the posterior pituitary and infundibulum resulting in diabetes insipidus and hyperprolactinaemia compared with a non-functioning pituitary adenoma.

  • The common associated symptoms of hypopituitarism due to lymphoma infiltration of the hypothalamic–pituitary system include painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms.

  • Radiological abnormalities of the hypothalamic–pituitary region are usually present and often associated with cavernous sinus or stalk involvement.

  • With early institution of definitive treatment, both haematological response and improvement of pituitary dysfunction are expected although the reversal of hypopituitarism tends to be partial and delayed.

  • A high index of suspicion of underlying malignancy such as lymphoma should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, radiological features atypical of pituitary adenomas and constitutional symptoms to enable early diagnosis and prompt initiation of definitive therapy.

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Casey M Hay Department of Obstetrics and Gynecology

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Daniel I Spratt Division of Reproductive Endocrinology and Infertility, Maine Medical Center, 22 Bramhall Street, Portland, Maine 04102, USA

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Summary

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.

Learning points

  • 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.

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