This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders ...characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders.
Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity, ...ectopic ossifications, and neurodevelopmental deficits, as well as hormonal resistance most prominently to parathyroid hormone (PTH). In addition to these alterations, patients may develop other hormonal resistances, leading to overt or subclinical hypothyroidism, hypogonadism and growth hormone (GH) deficiency, impaired growth without measurable evidence for hormonal abnormalities, type 2 diabetes, and skeletal issues with potentially severe limitation of mobility. PHP and related disorders are primarily clinical diagnoses. Given the variability of the clinical, radiological, and biochemical presentation, establishment of the molecular diagnosis is of critical importance for patients. It facilitates management, including prevention of complications, screening and treatment of endocrine deficits, supportive measures, and appropriate genetic counselling. Based on the first international consensus statement for these disorders, this article provides an updated and ready-to-use tool to help physicians and patients outlining relevant interventions and their timing. A life-long coordinated and multidisciplinary approach is recommended, starting as far as possible in early infancy and continuing throughout adulthood with an appropriate and timely transition from pediatric to adult care.
Context
Some reports suggest that acromegaly in elderly patients has a more benign clinical behavior and could have a better response to first-generation long-acting somatostatin receptor ligands ...(SRL). However, there is no specific therapeutic protocol for this special subgroup of patients.
Objective
This study aimed at identifying predictors of response to SRL in elderly patients.
Design
Multicentric retrospective nationwide study of patients diagnosed with acromegaly at or over the age of 65 years.
Results
One-hundred and eighteen patients (34 men, 84 women, mean age at diagnosis 71.7 ± 5.4 years old) were included. Basal insulin-like growth factor type 1 (IGF-1) above the upper limit of normal (ULN) and growth hormone (GH) levels (mean ± SD) were 2.7 ± 1.4 and 11.0 ± 11.9 ng/ml, respectively. The mean maximal tumor diameter was 12.3 ± 6.4 mm, and up to 68.6% were macroadenoma. Seventy-two out of 118 patients (61.0%) underwent surgery as primary treatment. One-third of patients required first-line medical treatment due to a rejection of surgical treatment or non-suitability because of high surgical risk. After first-line surgery, 45/72 (63.9%) were in disease remission, and 16/34 (46.7%) of those treated with SRL had controlled disease. Patients with basal GH at diagnosis ≤6 ng/ml had lower IGF-1 levels and had smaller tumors, and more patients in this group reached control with SRL (72.7% vs. 33.3%; p < 0.04) OR: 21.3, IC: 95% (2.4–91.1), while male patients had a worse response OR: 0.09, IC 95% (0.01–0.75). The predictive model curve obtained for SRL response showed an AUC of 0.82 CI (0.71–0.94).
Conclusions
The most frequent phenotype in newly diagnosed acromegaly in the elderly includes small adenomas and moderately high IGF-1 levels. GH at diagnosis ≤6 ng/ml and female gender, but not age
per se
, were associated with a greater chance of response to SRL.
Resumen Desde que en 1942 Albright y colaboradores describieran por primera vez el pseudohipoparatiroidismo como la existencia de hipocalcemia e hiperfosfatemia asociadas a resistencia tisular a la ...hormona paratiroidea (PTH) en presencia de una función renal normal, se han realizado grandes avances en la caracterización clínica y genética de los pacientes afectos de esta enfermedad. De hecho, no solo se han identificado las alteraciones moleculares responsables, sino que se ha podido establecer que variantes en otros genes de la misma vía de señalización, PTH/PTHrP a través de la proteína Gsα, son la causa de enfermedades que comparten determinadas manifestaciones clínicas con el pseudohipoparatiroidismo. En el ámbito pediátrico, los primeros síntomas o signos que deben hacernos pensar en alteraciones en esta vía son la presencia de osificaciones subcutáneas, la braquidactilia y/o la obesidad de inicio precoz, seguidas en el tiempo por la posible aparición de resistencia a la PTH. Esta sospecha clínica deberá ser confirmada mediante un diagnóstico molecular que permita el correcto seguimiento clínico coordinado y multidisciplinar. Entre los aspectos a tener en cuenta en la atención de estos pacientes se incluye la evaluación al diagnóstico y seguimiento de la eventual presencia de resistencia a la PTH y a la hormona tirotropa (TSH), deficiencia de hormona de crecimiento (GH), hipogonadismo, alteraciones esqueléticas, alteraciones de la salud dental, obesidad, resistencia a la acción de la insulina, intolerancia a la glucosa o diabetes mellitus tipo 2 e hipertensión, así como osificaciones ectópicas (subcutáneas o con afectación de tejidos más profundos) y alteración del desarrollo neurocognitivo.
Background: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism. Methodology: Adult patients with AIA who were ...followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves’ disease (n = 21), amiodarone-induced thyrotoxicosis (n = 7), and hyperfunctioning multinodular goiter (n = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil. Results: The median (IQR) time to development of agranulocytosis was 6.0 (4.0–11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves’ disease), and two patients died of septic shock secondary to AIA. Conclusions: AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously.
Background
Alemtuzumab is an effective therapy for relapsing multiple sclerosis. Autoimmune thyroid events are a common adverse event.
Objective
Describe endocrine and multiple sclerosis outcomes ...over 6 years for alemtuzumab-treated relapsing multiple sclerosis patients in the phase 3 CARE-MS I, II, and extension studies who experienced adverse thyroid events.
Methods
Endocrine and multiple sclerosis outcomes were evaluated over 6 years. Thyroid event cases, excluding those pre-existing or occurring after Year 6, were adjudicated retrospectively by expert endocrinologists independently of the sponsor and investigators.
Results
Thyroid events were reported for 378/811 (46.6%) alemtuzumab-treated patients. Following adjudication, endocrinologists reached consensus on 286 cases (75.7%). Of these, 39.5% were adjudicated to Graves’ disease, 2.5% Hashimoto's disease switching to hyperthyroidism, 15.4% Hashimoto's disease, 4.9% Graves’ disease switching to hypothyroidism, 10.1% transient thyroiditis, and 27.6% with uncertain diagnosis; inclusion of anti-thyroid antibody status reduced the number of uncertain diagnoses. Multiple sclerosis outcomes of those with and without thyroid events were similar.
Conclusion
Adjudicated thyroid events occurring over 6 years for alemtuzumab-treated relapsing multiple sclerosis patients were primarily autoimmune. Thyroid events were considered manageable and did not affect disease course. Thyroid autoimmunity is a common but manageable adverse event in alemtuzumab-treated relapsing multiple sclerosis patients.
ClinicalTrials.gov Registration Numbers: CARE-MS I (NCT00530348); CARE-MS II (NCT00548405); CARE-MS Extension (NCT00930553)
Cerebellar metastasis (CM) from papillary thyroid carcinoma (PTC) is exceptional with only 12 reported cases and usually carries a very poor prognosis. In the two previously reported patients in whom ...CM was detected before PTC, other distant or local metastases were already present by the time of PTC diagnosis. We report a patient found to have papillary thyroid microcarcinoma after surgical resection and histopathological study of a large solitary hemorrhagic CM, who showed no evidence of other metastatic sites and survived 7 years after initial diagnosis.
A 65-year-old female patient with a history of surgical resection of a 7-cm cerebellar mass diagnosed with PTC metastasis, and adjuvant treatment with cranial external radiotherapy, was referred to us. The neck ultrasonography showed a solitary 4-mm right thyroid nodule. Histopathology after total thyroidectomy revealed a 2-mm papillary thyroid microcarcinoma, sclerosing variant, with capsule infiltration but no regional lymph node invasion. Although she received a total dose of 500 mCi of 131-I after surgery and the last two whole-body scans were normal, serum thyroglobulin levels progressively increased. The patient refused any further test or treatment other than basal blood sampling and suppressive therapy with levothyroxine and remained stable for 4 years until she started to complain about deviation of her walk. A computed tomography scan showed a regrowth of the metastasis. She suffered a sudden worsening of her neurological status because of a big intratumoral hemorrhage that required decompressive craniectomy and hematoma evacuation surviving 3 years more after this episode.
To our knowledge, this is the first reported case of a solitary CM from an occult PTC, and also the first that developed an acute cerebellar hemorrhage years after cranial surgery, however, exhibiting the longest reported survival. This case highlights the importance of not only an appropriate initial treatment of the CM and primary PTC in these patients, but also a close follow-up, to avoid further complications and improve their prognosis.
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