Aldosterone-Producing Adenoma With a Somatic KCNJ5 Mutation Revealing APC-Dependent Familial Adenomatous Polyposis.

CONTEXT: Recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1, and ATP2B3 have been identified in aldosterone-producing adenomas (APAs). The question as to whether they are responsible for both nodulation and aldosterone production is not solved. CASE DESCRIPTION: We describe the case of a young patient who was diagnosed with severe arterial hypertension due to primary aldosteronism at age 26 years, followed by hemorrhagic stroke 4 years later. Abdominal computed tomography showed bilateral macronodular adrenal hyperplasia. Identification of lateralized aldosterone secretion led to right adrenalectomy, followed by normalization of biochemical and hormonal parameters and amelioration of blood pressure. The resected adrenal showed three nodules, one of them expressing aldosterone synthase and harboring a somatic KNCJ5 mutation. A Weiss revisited index of 3 of the APA prompted us to perform a second 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography after surgery, which revealed abnormal rectal activity despite the absence of clinical symptoms. Gastrointestinal exploration showed multiple polyps with severe dysplasia, and the diagnosis of familial adenomatous polyposis was established in the presence of a germline heterozygous APC gene mutation. Sequencing of somatic DNA from the APA and a second adrenal nodule revealed biallelic APC inactivation due to loss of heterozygosity in both nodules. CONCLUSIONS: This case report underlines the need for establishing the frequency of germline APC variants in patients with primary aldosteronism and bilateral macronodular adrenal hyperplasia because their presence may predispose to APA development and severe hypertension well before the first familial adenomatous polyposis symptoms appear. From a mechanistic point of view, it supports a two-hit model for APA development, whereby the first hit drives increased cell proliferation whereas the second hit specifies the pattern of hormonal secretion.

An unusual cause of cardiothyreosis.

Severe hyperthyroidism can cause cardiac complications, such as severe rhythm disturbances, heart failure and angina. Gestational trophoblastic disease (GTD) is a rare complication of pregnancy, ranging from benign hydatidiform mole to malignant form. Clinical hyperthyroidism may occur in GTD, as human chorionic gonadotropin (hCG) secreted by molar tissue is structurally similar to thyroid-stimulating hormone. Cardiothyreosis in this context is exceptional. We report the case of a nulligravida 42-year-old woman without thyroid or cardiac history who presented to the emergency department for dyspnoea. Examinations revealed an acute pulmonary oedema and sinus tachycardia. Serum hCG concentration was abnormally high (762 878 UI/l, N < 5). CT scan showed a voluminous uterine mass and eliminated pulmonary embolism. Cardiac output was increased in echocardiography. Complementary blood tests showed a peripheral hyperthyroidism. GTD was evoked in the context of uterine mass and high hCG concentration, which was responsible for inducing clinical hyperthyroidism and cardiothyreosis. A total hysterectomy was performed and histopathological examinations concluded to a non-invasive complete hydatidiform mole (begnin form). hCG fell to normal within 12 weeks, cardiac and thyroid functions normalized after mole evacuation.

Endocrine side-effects of anti-cancer drugs: the impact of retinoids on the thyroid axis.

Bexarotene (Targretin), approved since 1999 as a second-line treatment for late stage cutaneous T-cell lymphomas, has been shown to induce significant hypothyroidism through TSH suppression. This review revisits, through a case report, mechanisms by which rexinoids repress the expression of TSHB gene as well as αTSH and TRH genes. It appears that rexinoids suppress TSH independently from tri-iodothyronine. Bexarotene also differently affects the gene expression of deiodinases 1 and 2 as well as the peripheral clearance of thyroxine. These data might open new ways of research on the potential interaction between thyroid axis and endogenous rexinoids.

An isocaloric increase of eating episodes in the morning contributes to decrease energy intake at lunch in lean men.

The effects of increasing eating frequency on human health are unclear. This study used an integrated approach to assess the short-term consequences on appetite and metabolism. Twenty normal-weight men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180 min (F4), and followed by an ecological ad libitum buffet meal (T240) designed in an experimental restaurant. Intakes were assessed for the whole buffet meal and for each temporal quarter of the meal. (ii) two sessions consisting of the same two breakfasts F1 and F4 in a Clinical Investigation Centre. Blood sampling was performed to study the kinetics of ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, triglycerides and non-esterified fatty acids (NEFA). Substrate oxidation was measured by indirect calorimetry. During each of the 4 sessions, participants rated their appetite throughout the experiment. After F4, at T240 min, GLP-1 concentration was higher (P=0.006) while ghrelin concentration and hunger ratings were lower (P<0.001). We showed a trend for subjects to consume less energy (-88±61 kcal, P=0.08) at the buffet after F4, explained by a decrease in lipid intake (P=0.04). Marked differences in consumption were observed during the last temporal quarter of the meal for total energy and lipid intake (P=0.03). Mixed models highlighted differences between F1 and F4 for the kinetics of glucose, insulin and NEFA (P<0.001). The area under the curve was lower for insulin (P<0.001) and NEFA in F4 (P=0.03). Diet induced thermogenesis was reduced in F4 (P<0.05). This study demonstrated the beneficial short-term effect of increasing eating frequency on appetite in lean men considering subjective, physiological and behavioral data. However, the loss of the inter-prandial fast was associated with an inhibition of lipolysis, reflected by NEFA profiles, and a decrease in energy expenditure.