Clinical and pathologic characteristics of appendiceal neuroendocrine neoplasms diagnosed during pregnancy.

Introduction: Although appendicitis occurs in approximately 1:1000 pregnancies, appendiceal neuroendocrine neoplasm (ANEN) diagnosis during pregnancy is very rare. Data on presentation, treatment and prognosis is scarce. Aim: To describe ANEN cases diagnosed during pregnancy. Materials and methods: A retrospective appraisal of 7 consecutive ANEN patients diagnosed during pregnancy from four Israeli tertiary medical centers and comparison with 17 cases described in the literature from 1965-2021. Results: Age at ANEN diagnosis was 26.4 ± 3.5 years (range 21-33). Patients were diagnosed between gestational weeks 6-40, most frequently in the third trimester (53%). The most common presenting symptom was abdominal pain. Tumor size was 14.3 ± 8.9mm (range 3-45mm). In patients from our series appendiceal base involvement was reported in 2/7; mesoappendiceal invasion in 5/7; lympho-vascular invasion in 2/7. Ki67 staining was reported in 6/7 cases and ranged from 1-10%. Pathology details were lacking in most of the previously published cases. All 7 pregnancies in our series resulted in term delivery with no complications, whereas in historical cases there were one first trimester abortion, one ectopic pregnancy, and one stillbirth. Right hemicolectomy was performed in 5/7 patients in our series and reported in 2/17 historical cases. All hemicolectomies were performed after delivery, 3-16 months after appendectomy. Local metastases were reported in two cases. Follow-up duration was 7-98 months for our patients and 3-48 months in 5 historical cases. No disease recurrence, distant metastases or mortality were noted. Conclusions: To the best of our knowledge, this is the largest series describing the extremely rare diagnosis of ANEN during pregnancy. Although pathologic characteristics varied, pregnancy outcomes were usually favorable and long-term prognosis was excellent. This data may suggest that a conservative approach to patients with ANEN diagnosis during pregnancy can be considered.

Hyperprolactinemia diagnosis in elderly men: a cohort of 28 patients over 65 years.

PURPOSE: To characterize a cohort of elderly men with prolactinomas and their response to treatment. METHODS: We have identified 28 elderly men diagnosed after the age of 65 with prolactinomas at seven different endocrine clinics in Israel. A retrospective electronic chart review identified a control group of 76 younger men with macroprolactinomas treated in one of the centers. RESULTS: Mean age at diagnosis was 71.3 ± 5.6 (range 65-86) years, and current age 76.6 ± 7.5 years. Initial complaints leading to diagnosis included sexual dysfunction in 17 males (61%), headaches in two patients (7%), and visual abnormalities in two (7%). Three men presented with osteoporosis. Ten patients (36%) were diagnosed incidentally following brain imaging for unrelated reasons. Seventeen patients (61%) had macroadenoma, while eleven (39%) presented with a microadenoma or no visible adenoma. Mean prolactin (PRL) at presentation was 1594 (median 382; range 50-18,329) ng/ml. Testosterone was low in 21 men. Patients were treated with cabergoline (max dose, 1.1 ± 0.5 mg/week), except for one given bromocriptine; none required pituitary surgery or radiotherapy. Treatment normalized PRL in 24 patients, and in three men PRL suppressed to <2 ULN. Fifteen men normalized testosterone, three improved without normalization, and in three the normal baseline level increased. After a mean follow-up of 5.3 years, 14/15 patients harboring a macroadenoma showed significant adenoma shrinkage. Most patients reported improvement of low libido/erectile dysfunction. In the control group 60 men (79%) achieved PRL normalization. CONCLUSIONS: Elderly men with prolactinomas are diagnosed incidentally in 36% of cases. Long-term medical therapy is successful, achieving biochemical remission, adenoma shrinkage, and clinical improvement in almost all patients.

Thiazide Treatment in Primary Hyperparathyroidism-A New Indication for an Old Medication?

Context: There is no therapy for control of hypercalciuria in nonoperable patients with primary hyperparathyroidism (PHPT). Thiazides are used for idiopathic hypercalciuria but are avoided in PHPT to prevent exacerbating hypercalcemia. Nevertheless, several reports suggested that thiazides may be safe in patients with PHPT. Objective: To test the safety and efficacy of thiazides in PHPT. Design: Retrospective analysis of medical records. Setting: Endocrine clinic at a tertiary hospital. Patients: Fourteen male and 58 female patients with PHPT treated with thiazides. Interventions: Data were compared for each patient before and after thiazide administration. Main Outcome Measures: Effect of thiazide on urine and serum calcium levels. Results: Data are given as mean ± standard deviation. Treatment with hydrochlorothiazide 12.5 to 50 mg/d led to a decrease in mean levels of urine calcium (427 ± 174 mg/d to 251 ± 114 mg/d; P < 0.001) and parathyroid hormone (115 ± 57 ng/L to 74 ± 36 ng/L; P < 0.001), with no change in serum calcium level (10.7 ± 0.4 mg/dL off treatment, 10.5 ± 1.2 mg/dL on treatment, P = 0.4). Findings were consistent over all doses, with no difference in the extent of reduction in urine calcium level or change in serum calcium level by thiazide dose. Conclusion: Thiazides may be effective even at a dose of 12.5 mg/d and safe at doses of up to 50 mg/d for controlling hypercalciuria in patients with PHPT and may have an advantage in decreasing serum parathyroid hormone level. However, careful monitoring for hypercalcemia is required.

CENTRAL DIABETES INSIPIDUS: CLINICAL CHARACTERISTICS AND LONG-TERM COURSE IN A LARGE COHORT OF ADULTS.

OBJECTIVE: Central diabetes insipidus (CDI) is a rare heterogeneous condition with various underlying causes. This study sought to increase the still-limited data on the clinical characteristics and long-term course in adults diagnosed with CDI. METHODS: Data on demographics, presentation, imaging findings, affected pituitary axes, treatment, and complications were collected retrospectively from the files of 70 adult patients with CDI followed at a referral endocrine clinic. RESULTS: Forty women and 30 men were included. Mean age was 46.8 ± 15 years at the time of this study and 29.3 ± 20 years at CDI diagnosis. Twenty-eight patients were diagnosed in childhood. Forty patients (57%) acquired CDI following surgery. Main sellar pathologies were: craniopharyngioma, 17 patients (11 diagnosed in childhood); Langerhans histiocytosis, 10 patients (5 diagnosed in childhood); 7 patients (all diagnosed as adults) had a growth hormone-secreting adenoma; 12 patients (17%; 6 diagnosed in childhood) had idiopathic CDI. At least one anterior pituitary axis was affected in 73% of the cohort: 59% had growth hormone deficiency, 56% hypogonadism, 55% central hypothyroidism, 44% adrenocorticotropic hormone-cortisol deficiency. Patients with postoperative/trauma CDI (n = 44) tended to have multiple anterior pituitary axes deficits compared to the nonsurgical group of patients. All patients were treated with vasopressin preparations, mostly nasal spray. Hyponatremia developed in 32 patients, more in women, and was severe (<125 mEq/L) in 10 patients. Hypernatremia (>150 mEq/L) was noticed in 5 patients. Overall, the calculated complication rate was 22 in 1,250 treatment-years. CONCLUSION: Most adult patients with CDI have anterior pituitary dysfunction. Stability is usually achieved with long-term treatment. Women were more susceptible to desmopressin complications, albeit with an overall relatively low complication rate. ABBREVIATIONS: ACTH = adrenocorticotropic hormone CDI = central diabetes insipidus GH = growth hormone MRI = magnetic resonance imaging.

The serotonin syndrome: initial misdiagnosis.

BACKGROUND: The selective serotonin reuptake inhibitors are major drugs used in psychiatry today. While serotonin syndrome has become more frequent in an overdose situation and when an interacting drug is given, the toxicity of SSIRs is less than that of most other psychiatric drugs. Although the characteristics of toxicity are defined, it seems that physicians are not aware of the phenomenon. OBJECTIVES: To investigate patients with serotonin syndrome who were initially misdiagnosed. METHODS: We conducted a retrospective chart review of seven patients admitted in the last 2 years with mild to severe serotonin syndrome who were initially diagnosed as having other diseases. RESULTS: Most patients (5/7) were initially diagnosed with exacerbation of their psychiatric disorder. Gastroenteritis was diagnosed in two patients. One patient was suspected of having a metastatic lesion in the brain, and severe drug overdose was diagnosed in one patient. They all recovered after withholding the culprit drugs. CONCLUSIONS: This report is an addition to the growing literature on misdiagnosis of psychiatric patients. Serotonin toxicity should be considered in patients in whom the combination of mental changes, neuromuscular abnormalities and autonomic hyperactivity are features of acute disease.

Increased urinary Na-Cl cotransporter protein in familial hyperkalaemia and hypertension.

BACKGROUND: Familial hyperkalaemia and hypertension (FHH), also termed pseudohypoaldosteronism type II, is a rare monogenic form of hypertension caused by mutations in the WNK1 or WNK4 kinases. In vitro expression of WNK4 reduces surface abundance and activity of coexpressed NaCl cotransporter (NCCT). This effect is lost in disease-producing WNK4 mutants. In two mice models of FHH, one expressing two extra copies of mutant WNK4 (Q562E) and another in which a mutant (D561A) WNK4 replaced wild-type WNK4, renal distal tubule hyperplasia with overexpression of NCCT was found. Currently no FHH human renal tissue is available to test for increased distal tubule surface abundance of NCCT. The availability of a unique large family with FHH and the Q565E WNK4 mutation enabled us to investigate this issue in an indirect manner. METHODS: Assuming that shedding of NCCT to the urine reflects its abundance in the distal tubule epithelium, we measured urinary NCCT protein in eight subjects of the FHH family and in eight unrelated controls by western blotting. RESULTS: Urinary NCCT protein was about four times higher in FHH than in controls [111.1 +/- 40.5 versus 26.1 +/- 16.4 densitometry units (P < 0.0001)]. No significant difference in urinary sodium and potassium concentrations was seen between FHH and controls. CONCLUSIONS: The increased urinary NCCT in FHH most probably reflects increased NCCT abundance in the apical membrane of distal tubule cells in patients with FHH and the WNK4 mutation and points to the pathogenetic mechanism for the clinical phenotype of FHH and the WNK4 mutation, supporting results in transgenic mice with the same mutation and in knockin mice with another mutation.