Indeterminate thyroid nodules. The role of 18F-FDG PET/CT in the "era" of ultrasonography risk stratification systems and new thyroid cytology classifications.

PURPOSE: To evaluate the reliability of 18F-FDG PET/CT in distinguishing differentiated thyroid cancers (DTCs) and follicular neoplasms (FNs) from nodular hyperplasias (NH) in thyroid nodules with indeterminate cytology according to the Italian consensus for the classification and reporting of thyroid cytology (ICCRTC). We also tested whether the 18F-FDG PET/CT result was an independent risk factor for DTCs or FNs when sex, age, nodule dimensions, the European Thyroid Imaging and Reporting Data System (EU-TIRADS) and ICCRTC were considered. METHODS: We evaluated all patients with thyroid nodules and indeterminate cytology from September 2015 to May 2019; nodules were classified as low risk (TIR3A) and high risk (TIR3B) according to the ICCRTC. Neck ultrasonography features according to EU-TIRADS were re-evaluated and 18F-FDG PET/CT performed. All these patients were surgically treated. RESULTS: We included 111 patients; 67 nodules were classified as TIR3A and 44 as TIR3B. Overall, we found 27 DTCs, 57 NHs and 27 FNs. Among 73 FDG-negative nodules, we found four low-risk papillary thyroid cancers. All follicular thyroid cancers were identified by 18F-FDG-PET/CT. All TIR3A with low-risk US and negative 18F-FDG-PET/CT were NH. In TIR3A nodules, the sensitivity, specificity, negative and positive predictive values (NPV, PPV) of 18F-FDG PET/CT and EU-TIRADS for DTCs were 77.8%, 41.4%, 92.3%, 17.1% and 66.7%, 56.9%, 91.7%, 19.4%, respectively. In TIR3B nodules, the sensitivity, specificity, NPV and PPV of 18F-FDG PET/CT and EU-TIRADS for DTCs were 88.9%, 38.5%, 83.3%, 50% and 88.2%, 58.3%, 87.5%, 60%, respectively. On multivariate analysis, 18F-FDG-PET/CT (OR 9.04), ICCRTC (O.R. 7.57) and EU-TIRADS (OR 4.41) were all independent risk factors associated to DTCs and FNs. CONCLUSION: 18F-FDG-PET/CT is a reliable rule-out test for DTC even in thyroid nodules with indeterminate high-risk results. In this subgroup, PPV also tends to be considerable. 18F-FDG-PET/CT results, ICCRTC and EU-TIRADS proved independent risk factors associated to DTCs and FNs.

Unrecognized Pseudohypoparathyroidism Type 1A as a Cause of Hypocalcemia and Seizures in a 64-Year-Old Woman.

Pseudohypoparathyroidism type 1A (PHP1A) is usually diagnosed in childhood or early adulthood. We describe the case of a 64-year-old woman admitted to the Neurological Unit for recurrent episodes of loss of consciousness and seizures. Glycemia and ECG were normal, while hypocalcemia was noted. Clinical history revealed carpo-pedal spasm since the age of 30 years, cognitive impairment, hypothyroidism since early adulthood, and menopause at 30 years. She was taking oral calcium and cholecalciferol for chronic hypocalcemia. Physical features suggested Albright's osteodystrophy. Blood calcium was confirmed low, with increased parathyroid hormone, moderate 25OH-vitamin D deficiency, and normal creatinine. Brain CT scan revealed calcifications of the basal ganglia, cortical and subcortical white matter, and cerebellum. Therapy was switched to oral calcitriol, with normalization of calcium levels; levetiracetam was started and no further seizures occurred. The clinical diagnosis of PHP1A was confirmed by molecular analysis, which demonstrated the heterozygous c.568_571del mutation of the GNAS gene. Our report illustrates the natural history of a patient with PHP1A, which went undiagnosed until the age of 64 years, with multi-hormonal resistance and clinical sequelae evolving throughout life, and underlines the importance of diagnosing this rare disease, which has a great impact on patients and their family life.

[Thyrotoxic hypokalemic periodic paralysis: a rare complication of a common disease]. / Paralisi periodica ipopotassiemica tireotossica: una rara complicanza di una malattia comune.

Thyrotoxic periodic paralysis (TPP) is an uncommon but potentially lethal manifestation of hyperthyroidism characterized by muscle paralysis and hypokalemia. We have reported 3 cases of TPP in male patients, which manifested with morning muscle weakness evolved into paralysis. In all patients were found severe hypokalemia, abnormalities on electrocardiogram, and Graves' hyperthyroidism. Intravenous potassium administration led to normalization of potassium levels, and resolution of neurological symptoms. In addition, beta blockers and methimazole were started. Two patients required total thyroidectomy for poor control of hyperthyroidism with antithyroid drug. In patients presenting with periodic paralysis or diffuse muscle weakness thyroid function should be investigated in order to find out the cases secondary to unknown hyperthyroidism and to start an early appropriate combined therapy. The correct management of TPP can prevent serious cardiopulmonary complications.

Intrathyroidal parathyroid carcinoma as cause of hypercalcemia and pitfall of localization techniques: clinical and biologic features.

OBJECTIVE: To describe an unusual case of intrathyroidal parathyroid carcinoma (PC), which was retrospectively diagnosed in a woman who underwent surgical treatment of a recurrent nodular goiter. METHODS: We report the clinical and biologic features of an intrathyroidal PC, discuss the challenges with distinguishing PC from parathyroid adenoma, and review the related literature. RESULTS: A 67-year-old woman sought medical attention for dysphagia attributable to the recurrence of a normal functioning multinodular goiter. Thyroid ultrasonography disclosed a 3-cm solid inferior nodule. Because she refused surgical treatment and a trial of levothyroxine was unsuccessful, periodic follow-up examinations were scheduled. At 1-year follow-up, hypercalcemia (12.1 to 12.6 mg/dL) and low phosphorus levels (2.0 to 2.3 mg/dL) were found, and parathyroid hormone (PTH) levels were profoundly increased (481 to 721 pg/mL). Neck ultrasonography showed a large hypoechogenic solid nodule, not clearly cleaved from the right thyroid lobe, which was possibly compatible with an enlarged parathyroid gland; however, a sestamibi scan was negative. During total thyroidectomy, intraoperative frozen sections of the intrathyroid nodule were compatible with nodular goiter with cellular pleomorphism. Final histologic examination showed cellular nests with nuclear pleomorphism and invasive behavior into the thyroid tissue and likely into the vessels, in conjunction with immunohistochemical negativity for thyroglobulin and strong positivity for PTH. These findings were highly suggestive of and supported the diagnosis of PC. Postoperatively, calcium levels normalized, and PTH values declined considerably but remained slightly increased. Vitamin D supplementation helped normalize the PTH levels. The patient has undergone follow-up for 5 years and has shown no morphologic or biochemical signs of tumor recurrence. CONCLUSION: PC is a rare entity but should be suspected in patients with hypercalcemia, substantially increased PTH levels, and a neck mass. In such patients, techniques such as sestamibi scanning may fail to localize the neoplasm. Surgical treatment remains the preferred technique for an optimal outcome of the disease. Nevertheless, lifelong follow-up is necessary.

Clinically non-functioning pituitary macroadenomas in the elderly.

BACKGROUND AND AIMS: The aim of the present study was to evaluate the clinical presentation, characteristics and post-surgical outcome of non-functioning pituitary macroadenomas (NFPM) in elderly patients. METHODS: 27 patients (65-81 years; 13 Males, 14 Females) with NFPM (20-45 mm in diameter) were studied. The symptoms prompting neuroradiological studies were vision alterations in 52%, and dizziness, loss of memory, confusion, headache and depression in 29%; in 19% of patients, the disease was incidentally discovered during computed tomography (CT) or magnetic resonance imaging (MRI) for head trauma or cerebral ischemic attacks. RESULTS: Endocrinological evaluation on diagnosis showed global anterior hypopituitarism in 33% and partial hypopituitarism in 37% of patients. Immunohistochemistry showed signs of neurosecretion in most NFPM (chromogranin-A in 55%, gonadotropins in 19%, ACTH in 3.7%). Ki-67 antigen expression was indicative of low proliferative activity. Surgery was highly effective in improving alterations in vision and compressive symptoms, but was unable to restore normal pituitary function in established hypopituitarism in most cases. Eight patients (31%) were free of disease on subsequent MRI (follow-up 1-6 years). In 18 (69%) patients, a post-surgical residue was present. Of these, 6 (33%) underwent radiotherapy in the following years, owing to an increase in the volume of the remnants, and six (33%) underwent additional surgical treatment, followed by radiotherapy for further signs of growth in two. In the remaining patients, a small intrasellar remnant was stable on yearly MRI. CONCLUSIONS: in elderly patients, the development of hypopituitarism is often overlooked and the initial diagnosis of NFPM may be delayed. This can expose patients to the risks of unrecognized hypopituitarism and jeopardize post-surgical outcome.

[Acromegaly: multifaceted clinical presentation of a rare disease of the elderly. Report of two cases with long-term follow-up]. / Acromegalia: presentazione clinica eterogenea di una rara malattia dell'anziano. Descrizione di due casi con follow-up a lungo termine.

We report two cases of acromegaly in elderly patients. Both patients had markedly invasive GH-secreting macroadenomas, which caused hugely increased circulating GH levels (over 90 ng/ml). The first patient, 79 year-old, presented with goitre and severe osteoarthrosis, refused surgery and was treated with various somatostatin analogues (ultimately accompanied by cabergoline), without satisfactory control of the disease. The second patient, 67-year-old, presented with symptoms secondary to hypopituitarism, which had been previously misdiagnosed. These symptoms resolved with the appropriate substitutive therapy, which led to a significant improvement in her condition. However, two transphenoidal operations, radiotherapy and long-term somatostatin agonist therapy were required to control GH hypersecretion satisfactorily. The authors wish to underline that acromegaly is a rare but not negligible disorder in the elderly, which can affect the whole body functions and cause severe morbidities. In the two cases presented somatostatin agonists alone were not able to control the tumoral hypersecretion adequately. The prompt discovery (usually through a simple clinical evaluation) of this disease in the elderly, confirmed by hormonal and morphological evaluation, together with a multidisciplinary (medical, surgical, radiotherapeutic) approach can improve their quality of life and increase life expectancy.

[Screening for thyroid disorders in elderly patients]. / Screening per la funzionalità tiroidea nei pazienti anziani ricoverati.

In elderly patients, thyroid diseases may remain undiagnosed due to the lack of specificity of the clinical presentation. Thyroid function alterations seem to be more common in older persons than in adults. The aim of our study was to evaluate the incidence of thyroid function alterations in 300 elderly patients admitted to the division of Internal Medicine of the local hospital in Levanto, in a one-year period. Thyroid function alterations were discovered in 12.6% of the patients and considering the group of patients in whom a thyroid function alteration was demonstrated, 45% of them were affected by hypothyroidism (10.7% overt primary hypothyroidism, 28.9% sub-clinical hypothyroidism, 5.4% hypothyroidism secondary to hypopituitarism), 15.6% by hyperthyroidism (overt 7.8% , subclinical 7.8%), and 39.4% showed a low T3 syndrome. Our data confirm the high incidence of previously unrecognized thyroid diseases in the elderly patients admitted to an hospital and the profit that these patients can receive from the appropriate diagnosis at the admission and justify the cost of routine testing for FT4 and TSH in every person at hospital admission.