The elevated incidence of DTC in patients with TSHoma suggests a possible role of TSH hypersecretion in the development of thyroid tumors. A formal high-resolution ultrasound of the thyroid is recommended in patients diagnosed with a TSHoma, especially if a long history of the pituitary tumor is suspected. Moreover, suspicion about the presence of TSHoma should be raised by the lack of suppression of TSH levels despite adequate doses of levothyroxine after thyroidectomy for DTC.

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SummaryACTH-secreting pheochromocytoma is a very rare cause of Cushing’s syndrome, with a high morbidity and mortality risk due to both cortisol and catecholamines excess. We report the case of a 45-year-old female patient with a 3 cm, high-density, left adrenal mass, diagnosed as an ACTH-secreting pheochromocytoma. The biochemical sensitivity of the tumor to somatostatin analogues was tested by a 100 μg s.c. octreotide administration, which led to an ACTH and cortisol reduction of 50 and 25% respectively. In addition to alpha and beta blockers, preoperative approach to laparoscopic adrenalectomy included octreotide, a somatostatin analogue, together with ketoconazole, in order to achieve an adequate pre-surgical control of cortisol release. Histopathological assessment confirmed an ACTH-secreting pheochromocytoma expressing type 2 and 5 somatostatin receptors (SSTR-2 and -5).Learning points:ACTH-secreting pheochromocytomas represent a rare and severe condition, characterized by high morbidity and mortality risk.Surgical removal of the adrenal mass is the gold standard treatment, but adequate medical therapy is required preoperatively to improve the surgical outcome and to avoid major complications.Somatostatin analogs, in addition to other medications, may represent a useful therapeutic option for the presurgical management of selected patients.In this sense, the octreotide challenge test is a useful tool to predict favorable therapeutic response to the treatment.

Primary objective was to evaluate whether an intensified insulin therapy (IIT) incorporating the target of normal fasting glucose and HbA1c levels could halve the incidence of restenosis/amputation/SCA/death at 6 months after peripheral angioplasty compared with standard care (SC) in patients with type 2 diabetes (DMT2) affected by critical limb ischemia (CLI). Forty-six consecutive patients with DMT2 and CLI were randomly assigned to a parallel, open-label study with IIT (basal-bolus glulisine + glargine administrations) or SC (glargine administration + oral antidiabetic drugs). A SNP of eNOS (rs753482-A>C) and circulating CD34(+) and CD34(+)KDR(+) progenitor cells were determined. At the end of the study, although HbA1c levels were lower in IIT than in SC (6.9 ± 1.3 % vs. 7.6 ± 1.2 %, p < 0.05), IIT did not reduce the cumulative incidence of restenosis/amputation/SCA/death (52 and 65 %, respectively, odd ratio 0.59; CI 95 %: 0.21-1.62, p = 0.59). rs753482AC+CC as compared with rs753482AA increased the cumulative incidence of restenosis/amputation/SCA/death (79 and 42 %; odd ratio 5.3; CI 95 %: 1.41-19.5, p < 0.02). Baseline CD34(+)KDR(+) were higher in rs753482AA (166.2 ± 154.0 × 10(6) events) than in rs753482AC+CC (63.1 ± 26.9 × 10(6) events, p < 0.01). At the end of the study, the highest circulating CD34(+)KDR(+) were found in IIT rs753482AA (246.9 ± 194.0 × 10(6) events) while the lowest levels were found in SC rs753482AC+CC (70.9 ± 45.0 × 10(6) events). IIT did not decrease the cumulative incidence of restenosis/amputation/SCA/death in DMT2 and CLI patients. These patients correspond to a class of fragile subjects at high risk of cardiovascular events, and new predictors of restenosis should be contemplated, such as of eNOS polymorphism, (rs753482-A>C SNP) and circulating endothelial progenitor cells.

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Purpose: The effects of growth hormone (GH) replacement on bone mass and body composition in adult with GH de ciency (AGHD) are still debated with regard to their persistence in the long term. Moreover, the impact of gender on the response to GH is controversial. Aim of this study was to evaluate the long-term effects of rhGH replacement on bone mass and body composition in a monocentric cohort of patients with AGHD.Methods: Data from 138 patients with AGHD (34.3 ± 14.3 years, 48 women and 90 men) treated with rhGH for a period of at least 3 years up to a maximum of 10 were retrospectively collected. Bone mineral density (BMD) at the lumbar spine, femur, and radius, and total and truncular body composition were evaluated by dual energy X-ray absorption (DXA) before and during treatment. Clinical and laboratory evaluations were performed before and during the treatment period on an annual basis.Results: Lumbar spine BMD consistently increased in males, while in females decreased after a transient improvement observed during the rst 4 years of therapy. There were no signi cant changes in femoral BMD in either sexes, while a progressive increase at radius was observed only in males. Lean mass signi cantly increased in both sexes, while fat mass decreased only in males.Conclusions: In AGHD patients long-term rhGH replacement therapy induces a positive effect with regard to bone mass and body composition. A sexual dimorphism in the response to treatment is evident, with males displaying more favorable outcome.

Context Several case reports of Graves’ disease (GD) occurrence after COVID-19 vaccination were recently published and possibly related to the autoimmune syndrome induced by adjuvants (ASIA). The aim of our study was to evaluate possible distinctive features in the presentation and clinical course of patients with GD occurring early (within 4 weeks) after COVID-19 vaccination who attended our Endocrine Unit in 2021. Design Patients with first episode of GD attending a tertiary endocrine center between January 1st and December 31st 2021 were included. Results Sixty-four patients with first episode of GD were seen in 2021: 20 (31.2%) of them had onset within 4 weeks following vaccine administration. Compared to the other 44 patients, the 20 patients with post-vaccine early-onset (PoVEO) GD were older (median age: 51 years vs 35 years, p = 0.003) and more likely male (40.0% vs 13.6%, p = 0.018). At diagnosis, the biochemical and immune profiles were similar between the two groups. However, at 3 months after starting methimazole, PoVEO GD patients had significantly lower TRAb titer and were taking lower doses of methimazole than the other GD patients. None in the PoVEO group had sustained fT3 elevation. Conclusions This relatively large series suggests that in 2021, PoVEO GD may be a new nosological entity representing one third of patients evaluated for new-onset GD in our center. Distinctive features included older age at onset, higher male prevalence and a better initial biochemical and immunological response to treatment. Further studies are warranted to clinically and biochemically differentiate these cases from sporadically occurred GD.

IntroductionThe bone matrix protein osteocalcin (OC), secreted by osteoblasts, displays endocrine effects. We tested the hypothesis that OC modulates parathyroid tumor cell function.MethodsPrimary cell cultures derived from parathyroid adenomas (PAds) and HEK293 cells transiently transfected with the putative OC receptor GPRC6A or the calcium sensing receptor (CASR) were used as experimental models to investigate γ-carboxylated OC (GlaOC) or uncarboxylated OC (GluOC) modulation of intracellular signaling.ResultsIn primary cell cultures derived from PAds, incubation with GlaOC or GluOC modulated intracellular signaling, inhibiting pERK/ERK and increasing active β-catenin levels. GlaOC increased the expression of PTH, CCND1 and CASR, and reduced CDKN1B/p27 and TP73. GluOC stimulated transcription of PTH, and inhibited MEN1 expression. Moreover, GlaOC and GluOC reduced staurosporin-induced caspase 3/7 activity. The putative OC receptor GPRC6A was detected in normal and tumor parathyroids at membrane or cytoplasmic level in cells scattered throughout the parenchyma. In PAds, the membrane expression levels of GPRC6A and its closest homolog CASR positively correlated; GPRC6A protein levels positively correlated with circulating ionized and total calcium, and PTH levels of the patients harboring the analyzed PAds. Using HEK293A transiently transfected with either GPRC6A or CASR, and PAds-derived cells silenced for CASR, we showed that GlaOC and GluOC modulated pERK/ERK and active β-catenin mainly through CASR activation.ConclusionParathyroid gland emerges as a novel target of the bone secreted hormone osteocalcin, which may modulate tumor parathyroid CASR sensitivity and parathyroid cell apoptosis.