Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, primary hyperparathyroidism, and pheochromocytoma. Multiple endocrine neoplasia type 2 is still an underdiagnosed, or late-diagnosed condition in many areas of the world. Since 1993, when the first missense RET proto-oncogene (RET) mutations were reported in MEN2, up to 46 different RET-causing disease mutations have been described. Since a strong genotype-phenotype correlation exists for MEN2, the detection of RET mutations has produced a major impact in early recognition and treatment of MTC and MEN2. Presently, RET mutation analysis should be performed for all MEN2 cases and their at-risk familial relatives. Further, prophylactic total thyroidectomy is indicated in all cases harboring activating gametic RET mutations. In most RET mutation carriers, prophylactic total thyroidectomy is indicated at ages as early as a few months to 4 years of age, promoting longer survival and improvement of quality of life or even definitive cure. We discuss the large impact of RET proto-oncogene analysis on the clinical management of MEN2 and the role of early RET molecular DNA diagnosis in providing clinicians and surgeons with valuable information that enables them to indicate early total thyroidectomy.

Most cases of sporadic primary hyperparathyroidism present disturbances in a single parathyroid gland and the surgery of choice is adenomectomy. Conversely, hyperparathyroidism associated with multiple endocrine neoplasia type 1 (hyperparathyroidism/multiple endocrine neoplasia type 1) is an asynchronic, asymmetrical multiglandular disease and it is surgically approached by either subtotal parathyroidectomy or total parathyroidectomy followed by parathyroid auto-implant to the forearm. In skilful hands, the efficacy of both approaches is similar and both should be complemented by prophylactic thymectomy. In a single academic center, 83 cases of hyperparathyroidism/ multiple endocrine neoplasia type 1 were operated on from 1987 to 2010 and our first surgical choice was total parathyroidectomy followed by parathyroid auto-implant to the non-dominant forearm and, since 1997, associated transcervical thymectomy to prevent thymic carcinoid. Overall, 40% of patients were given calcium replacement (mean intake 1.6 g/day) during the first months after surgery, and this fell to 28% in patients with longer follow-up. These findings indicate that several months may be needed in order to achieve a proper secretion by the parathyroid auto-implant. Hyperparathyroidism recurrence was observed in up to 15% of cases several years after the initial surgery. Thus, long-term follow-up is recommended for such cases. We conclude that, despite a tendency to subtotal parathyroidectomy worldwide, total parathyroidectomy followed by parathyroid auto-implant is a valid surgical option to treat hyperparathyroidism/multiple endocrine neoplasia type 1. Larger comparative systematic studies are needed to define the best surgical approach to hyperparathyroidism/multiple endocrine neoplasia type 1.

Introduction: The clinical management of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) stages G3‑G4 patients currently faces several challenges. Although the understanding of SHPT has increased exponentially in recent years, many aspects regarding its diagnosis and management in non‑dialysis G3‑G4 CKD remain elusive. Specifically, while it is known that SHPT is linked to vitamin D insufficiency in pre‑dialysis CKD patients, the target levels of vitamin D and parathyroid hormone, SHPT, and vitamin D monitoring and therapeutic guidelines are still to be clarified. It is, consequently, of utmost importance to generate data supporting consensual clinical decision‑making and the implementation of evidence‑based clinical practice guidelines. Methods: Thus, a single‑round Delphi‑like study was conducted herein to assess the opinions and the level of agree‑ ment of 59 Portuguese nephrologists on the diagnosis and treatment of pre‑dialysis G3‑G4 CKD patients with SHPT. Results: Although none of the statements under analysis gathered consensus, more than half of the statements regarding SHPT monitoring and therapeutics focusing on G3‑G4 CKD achieved a qualified majority of agreement/disagreement. Overall, it may indicate a growing consensus trend among Portuguese nephrology specialists. Conversely, the heterogeneity of participants’ opinions regarding the treatment of SHPT‑associated vitamin D insufficiency reflects the heterogeneity in the knowledge in this specific field. Conclusion: The results from this Delphi‑like panel represent a first step towards improving the monitoring and thera‑ peutic strategies concerning the prognosis of G3‑G4 CKD patients, fostering unison among the Portuguese nephrology community.

Durante a gravidez e aleitamento ocorrem alterações significativas no metabolismo fosfocálcico, e, consequentemente, na fisiologia esquelética materna, a fim de se satisfazer as exigências do feto e recém-nascido. O conhecimento da homeostase do metabolismo fosfocálcico é essencial para se proceder ao adequado diagnóstico e gestão do hiperparatiroidismo primário (HPTp), distúrbio que apresenta um quadro clínico caracterizado por níveis de hormona paratiroide (PTH) significativamente elevados, hipercalcemia e hipofosfatemia. Sendo uma condição patológica agravada progressivamente com o tempo caso não haja intervenção cirúrgica. O hiperparatiroidismo desencadeia, frequentemente, osteoporose, nefrolitíase associada a cólicas renais, nefrocalcinose, hipertensão e arritmias cardíacas. A presente dissertação serve de revisão científica sobre o metabolismo fosfocálcico na gravidez e aleitamento, delineando detalhadamente, para tal, os mecanismos de absorção e excreção do fósforo e do cálcio, identificando e interrelacionando os principais componentes que regulam estes macrominerais, e explorando a importância da manutenção da homeostase do metabolismo fosfocálcico, a fim de melhor compreender a componente fisiológica e fisiopatológica e prevenir distúrbios passíveis de ocorrerem durante a gestação e lactação. Detalhadamente, a tese em questão aborda o HPTp, uma patologia paratiroideia, refletindo acerca das várias opções viáveis de modo a concretizar um melhor diagnóstico, uma gestão contínua, e um tratamento adequado do distúrbio, especialmente durante a gravidez.

Primary hyperparathyroidism _HPT. is associated with generalized skeletal changes, its full-blown osseous manifestations known as osteitis fibrosa cystica. Fibrous dysplasia _FD., a benign bone disorder, is differentiated from generalized fibrocystic disease caused by hyperparathyroidism. The classic triad of McCune–Albright syndrome includes polyostotic FD, patchy skin pigmentation, and sexual precocity. Other associated endocrinopathies are hyperthyroidism, Cushing’s syndrome, acromegaly, and HPT. We describe a patient with severe generalized and focal bone lesions and sexual precocity. HPT was diagnosed and treated with persistence of cystic bone lesions. The similarities between HPT and FD are discussed, focusing on a possible genetically determined mechanism to explain the relationship between them.

Parathyroid hormone (PTH) plays a critical role in calcium and phosphorus metabolism. Interestingly, in two forms of hyperparathyroidism (excessive amount of PTH in the serum), the metabolic disturbances in patients with chronic kidney disease (CKD) significantly differ from those with primary hyperparathyroidism (PHP). Since an intuitive understanding of these PTH-linked regulatory mechanisms are hardly possible, we developed a mathematical model using clinical data (1586 CKD and 40 PHP patients). The model was composed of a set of ordinary differential equations, in which the regulatory mechanism of PTH together with other key factors such as 1,25-Dihydroxyvitamin D (1,25(OH)₂D) and calcium was described in the tissues including bone, the kidney, the serum, and the parathyroid glands. In this model, an increase in PTH was induced by its autonomous production in PHP, while PTH in CKD was elevated by a decrease in feedback inhibition of 1,25(OH)₂D in the serum, as well as an increase in stimulation by phosphorus in the serum. The model-based analysis revealed characteristic differences in the outcomes of hyperparathyroidism in CKD and PHP. The calcium exchange in bone, for instance, was predicted significantly higher in PHP than CKD. Furthermore, we evaluated the observed and predicted responses to the administration of calcimimetics, a recently developed synthetic drug that modulated efficacy of calcium-sensing receptors. The results herein support the notion that the described model would enable us to pose testable hypotheses about the actions of PTH, providing a quantitative analytical tool for evaluating treatment strategies of PHP and CKD.

As doenças endócrinas são comuns nos cães, e muitas delas apresentam manifestações oculares. Os cães com diabetes mellitus desenvolvem frequentemente cataratas, mas também podem apresentar outras alterações oculares, como queratoconjuntivite seca, edema e úlceras da córnea, hiperlipidemia ocular e retinopatias. Na síndrome de Cushing podem ser observados queratoconjuntivite seca, úlceras da córnea, calcificação distrófica da córnea, hiperlipidemia, síndrome de degenerescência adquirida súbita da retina (SARDS), alterações neuro-oftalmológicos e retinopatia hipertensiva. Na doença de Addison, a hipercalcemia secundária pode originar calcificação metastática dos tecidos oculares. O hipotiroidismo pode originar hiperlipidemia ocular, queratoconjuntivite seca, paralisia facial e retinopatia hipertensiva, enquanto o hipertiroidismo pode causar retinopatia e calcificação metastática dos tecidos oculares. Distúrbios da glândula paratiróide podem provocar cataratas em casos de hipocalcemia, ou calcificação metastática se hipercalcemia. O conhecimento das manifestações oculares de doenças endócrinas é importante porque podem comprometer a qualidade de vida do animal, e por isso devem ser avaliadas, diagnosticadas e tratadas o mais precocemente possível. Para além disso, a sua identificação pode também ajudar no diagnóstico da doença primária.

ABSTRACT Fibromyalgia (FM) and hyperparathyroidism may present similar symptoms (musculoskeletal pain, cognitive disorders, insomnia, depression and anxiety), causing diagnostic confusion. Objectives: To determine the frequency of asymptomatic hyperparathyroidism in a sample of patients with FM and to evaluate the association of laboratory abnormalities to clinical symptoms. Methods: Cross-sectional study with 100 women with FM and 57 healthy women (comparison group). Parathyroid hormone (PTH), calcium and albumin levels were accessed, as well as symptoms in the FM group. Results: In FM group, mean serum calcium (9.6 ± 0.98 mg/dL) and PTH (57.06 ± 68.98 pg/mL) values were considered normal, although PTH levels had been significantly higher than in the comparison group (37.12 ± 19.02 pg/mL; p = 0.001). Hypercalcemic hyperparathyroidism was diagnosed in 6% of patients with FM, and 17% of these women exhibited only high levels of PTH, featuring a normocalcemic hyperparathyroidism, with higher frequencies than those expected for their age. There was no significant association between hyperparathyroidism and FM symptoms, except for epigastric pain, which was more frequent in the group of patients concomitantly with both diseases (p = 0.012). Conclusions: A high frequency of hyperparathyroidism was noted in women with FM versus the general population. Normocalcemic hyperparathyroidism was also more frequent in patients with FM. Longitudinal studies with greater number of patients are needed to assess whether this is an association by chance only, if the increased serum levels of PTH are part of FM pathophysiology, or even if these would not be cases of FM, but of hyperparathyroidism.

ABSTRACT Background: Persistent hyperparathyroidism post-transplant is associated with increases in the incidence of cardiovascular events, fractures, and deaths. The aim of this study was to compare both therapeutic options available: parathyroidectomy (PTX) and the calcimimetic agent cinacalcet. Methods: A single center retrospective study including adult renal transplant recipients who developed hypercalcemia due to persistent hyperparathyroidism. Inclusion criteria: PTH > 65 pg/mL with serum calcium > 11.5 mg/dL at any time after transplant or serum calcium persistently higher than 10.2 mg/dL one year after transplant. Patients treated with cinacalcet (n=46) were compared to patients treated with parathyroidectomy (n=30). Follow-up period was one year. Clinical and laboratory data were analyzed to compare efficacy and safety of both therapeutic modalities. Results: PTX controlled calcemia faster (month 1 x month 6) and reached significantly lower levels at month 12 (9.1±1.2 vs 9.7±0.8 mg/dL, p < 0.05); PTX patients showed significantly higher levels of serum phosphate (3.8±1.0 vs 2.9±0.5 mg/dL, p < 0.05) and returned PTH to normal levels (45±51 pg/mL). Cinacalcet, despite controlling calcium and phosphate in the long term, decreased but did not correct PTH (197±97 pg/mL). The proportion of patients that remained with PTH above normal range was 95% in the cinacalcet group and 22% in the PTX group. Patients treated with cinacalcet had better renal function (creatinine 1.2±0.3 vs 1.7±0.7 mg/dL, p < 0.05). Conclusions: Surgical treatment was superior to cinacalcet to correct the metabolic disorders of hyperparathyroidism despite being associated with worse renal function in the long term. Cinacalcet proved to be a safe and well tolerated drug.