Gloria Tsvetov

Impact of Pregnancy on Outcome and Prognosis of Survivors of Papillary Thyroid Cancer

BACKGROUND Papillary thyroid cancer (PTC) commonly affects women of child-bearing age. During normal pregnancy, several factors may have a stimulatory effect on normal and nodular thyroid growth. The aim of the study was to determine whether pregnancy in thyroid-cancer survivors poses a risk of progression or recurrence of the disease. METHODS The files of 63 consecutive women who were followed at the Endocrine Institute for PTC in 1992-2009 and had given birth at least once after receiving treatment were reviewed for clinical, biochemical, and imaging data. Thyroglobulin levels and neck ultrasound findings were compared before and after pregnancy. Demographic and disease-related characteristics and levels of thyroid-stimulating hormone (TSH) during pregnancy were correlated with disease persistence before conception and disease progression during pregnancy using Pearsons analysis. RESULTS Mean time to the first delivery after completion of thyroid-cancer treatment was 5.08 ± 4.39 years; mean duration of follow up after the first delivery was 4.84 ± 3.80 years. Twenty-three women had more than one pregnancy, for a total of 90 births. Six women had evidence of thyroid cancer progression during the first pregnancy; one of them also showed disease progression during a second pregnancy. Another two patients had evidence of disease progression only during their second pregnancy. Mean TSH level during pregnancy was 2.65 ± 4.14 mIU/L. There was no correlation of disease progression during pregnancy with pathological staging, interval from diagnosis to pregnancy, TSH level during pregnancy, or thyroglobulin level before conception. There was a positive correlation of cancer progression with persistence of thyroid cancer before pregnancy and before total I-131 dose was administered. CONCLUSIONS Pregnancy does not cause thyroid cancer recurrence in PTC survivors who have no structural or biochemical evidence of disease persistence at the time of conception. However, in the presence of such evidence, disease progression may occur during pregnancy, yet not necessarily as a consequence of pregnancy. The finding that a nonsuppressed TSH level during pregnancy does not stimulate disease progression suggests that it may be an acceptable therapeutic goal in this setting.

Influence of number of deliveries and total breast-feeding time on bone mineral density in premenopausal and young postmenopausal women

OBJECTIVES Pregnancy and lactation have been associated with decline in bone mineral density (BMD). It is not clear if there is a full recovery of BMD to baseline. This study sought to determine if pregnancy or breast-feeding or both have a cumulative effect on BMD in premenopausal and early postmenopausal women. STUDY DESIGN We performed single-center cohort analysis. Five hundred women aged 35-55 years underwent routine BMD screening from February to July 2011 at a tertiary medical center. Patients were questioned about number of total full-term deliveries and duration of breast-feeding and completed a background questionnaire on menarche and menopause, smoking, dairy product consumption, and weekly physical exercise. Weight and height were measured. Dual-energy X-ray absorptiometry was used to measure spinal, dual femoral neck, and total hip BMD. MAIN OUTCOME MEASURES Associations between background characteristics and BMD values were analyzed. RESULTS Sixty percent of the women were premenopausal. Mean number of deliveries was 2.5 and mean duration of breast-feeding was 9.12 months. On univariate analysis, BMD values were negatively correlated with patient age (p=0.006) and number of births (p=0.013), and positively correlated with body mass index (p<0.001). On multiple (adjusted) logistic regression analysis, prolonged breast-feeding duration, but not number of deliveries, was significantly correlated to a low BMD (p=0.008). An effect was noted only in postmenopausal women. The spine was the most common site of BMD decrease. CONCLUSIONS Prolonged breast-feeding may have a deleterious long-term effect on BMD and may contribute to increased risk of osteoporosis later in life.

Pregnancy Outcomes in Women With Primary Hyperparathyroidism

OBJECTIVE Primary hyperparathyroidism (PHPT) during pregnancy may pose considerable risks to mother and fetus. This study examined pregnancy outcomes in women with gestational PHPT in relation to clinical and laboratory parameters. DESIGN This study was designed as a retrospective case series. METHODS The study group included 74 women aged 20-40 years who were diagnosed with PHPT after a finding of serum calcium ≥ 10.5 mg/dL on routine screening at a health maintenance organization (2005-2013) and who became pregnant during the time of hypercalcemia (124 pregnancies). Clinical and laboratory data were collected from the files. Pregnancy outcomes were compared with 175 normocalcemic pregnant women (431 pregnancies) tested during the same period. RESULTS The cohort represented 0.03% of all women of reproductive age tested for serum calcium during the study period. Abortion occurred in 12 of 124 pregnancies (9.7%), and other complications occurred in 19 (15.3%) with no statistically significant differences from controls. Hypercalcemia was first detected during pregnancy in 14 of 74 women (18.9%) and before pregnancy (mean, 33.4 ± 29 mo) in 60. Serum calcium was measured antenatally in 57 of 124 pregnancies (46%); the mean level was 10.7 ± 0.6 mg/dL (median, 10.6 mg/dL). Measurement of the serum PTH level (with consequent diagnosis of PHPT) was performed during the first studied pregnancy in 17 of 74 women (23%), before pregnancy (mean, 37.8 ± 25.5 mo; median, 34 mo) in 23 (31.1%), and after delivery (mean, 54.7 ± 45.7 mo; median, 35 mo) in 34 (45.9%). Forty-three women (58.1%) underwent parathyroidectomy, six during pregnancy, without maternal or fetal complications. No difference was found in abortion or any pregnancy-related complication between patients who subsequently underwent parathyroidectomy and those who did not. No significant correlation was found between calcium level during pregnancy and pregnancy outcomes. CONCLUSIONS Serum calcium levels are usually only mildly elevated during pregnancy in women with PHPT. A significant proportion of cases go undiagnosed. Mild hypercalcemia in gestational PHPT is generally not associated with an increased risk of obstetrical complications.

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.

Cushing’s syndrome: comparison between Cushing’s disease and adrenal Cushing’s

PurposeThe most common etiology of Cushing’s syndrome (CS) is an ACTH-producing pituitary adenoma (pitCS), reported as 2–3 times more frequent than primary adrenal CS (adrCS). We aimed to analyze and compare features of patients with pitCS and adrCS.MethodsA retrospective file review of 196 consecutive patients (age 46.8 ± 15.6 years, 76% female) diagnosed with CS in 2000–2017 and followed for 5.2 ± 4.2 years; 109 (55.6%) had pitCS and 76 (38.8%) adrCS. Epidemiologic, clinical and biochemical factors were compared between and within the pitCS and adrCS groups.ResultsThe relative proportion of pitCS to adrCS (1.4) was lower than previously reported and gradually decreased during the study years to only 1.2 in 2012–2017. The most common reason for CS screening was weight-gain in the pitCS group (48.6%) and adrenal incidentaloma in the adrCS group (39.5%). The pitCS patients were diagnosed at younger age (42.5 ± 15.1 vs. 51.6 ± 15.1 years, p < 0.001) and had lower prevalence of hypertension (51.4 vs. 74%, p = 0.005). There was no between-group difference in severity of hypercortisoluria. Within the adrCS group, patients diagnosed after detection of an adrenal incidentaloma had milder hypercortisoluria than the remaining patients, presented with smaller adrenal lesions (35.9 ± 16.3 vs. 49.1 ± 33.7 cm, p = 0.04), and received post-adrenalectomy glucocorticoid treatment for shorter periods (13 ± 11.6 vs. 31 ± 40 months, p = 0.04).ConclusionsThe relative proportion of adrCS to pitCS is rising, probably because of an increasing detection of cortisol-secreting adrenal incidentalomas associated with milder hypercortisolism. There is no difference between pitCS and adrCS in the severity of hypercortisoluria, although significant clinical differences were found.

LONG-TERM OUTCOMES AND PROGNOSTIC FACTORS IN PATIENTS WITH DIFFERENTIATED THYROID CANCER AND DISTANT METASTASES

OBJECTIVE Distant metastatic spread is the most frequent cause of thyroid cancer-related death. The objective of this study was to evaluate overall and disease-related survival of patients with differentiated thyroid cancer (DTC) and distant metastases (DM) attending a single medical center and to investigate variables predictive of better long-term outcomes. METHODS The Rabin Medical Center Thyroid Cancer Registry was searched for patients with DM from DTC. RESULTS The cohort included 138 patients (58.7% female) diagnosed at age 54.7 ± 19.5 years. Mean primary tumor size was 33.9 ± 26 mm. Most patients (57.7%) were stage T3/T4; 48.7% had extrathyroidal extension; 53.5% had lymph node metastases. Histopathology yielded papillary and follicular thyroid carcinoma in 66.7% and 13.8%, respectively, and intermediate/poorly differentiated carcinoma in 19.6%. All but 2 patients underwent total thyroidectomy, and 133/138 (96.4%) received radioactive iodine (RAI) therapy. DM were synchronous in 55.1%. The mean follow-up was 8.2 years from detection of metastases. The common sites of metastases were the lungs (85.6% of patients), bones (39.9%), brain (5.8%) and liver (3.6%). At last follow-up, resolution was documented in 24.6% of patients, improvement/stable disease in 31.6%, and structurally progressive disease in 43.4%. By the end of the study, 40.6% of patients died, 23.2% of DTC. Improved overall survival and disease progression were associated with younger age, lung-only DM, and metastatic RAI avidity. CONCLUSION Patients with DTC and DM treated by standard-of-care approaches frequently achieve favorable long-term outcomes. Novel therapies might be necessary in only a minority of these patients, and the reported prognostic factors can aid in their identification. ABBREVIATIONS CR = complete response; DM = distant metastases; DTC = differentiated thyroid cancer; ETE = extra-thyroidal extension; M0 = detected during follow-up; M1 = detected at diagnosis; MSKCC = Memorial Sloan Kettering Cancer Center; NED = no evidence of disease; OS = overall survival; PFS = progression free survival; PTC = papillary thyroid cancer; RAI = radioactive iodine; Tg = thyroglobulin.

VARIATIONS IN CLINICAL AND IMAGING FINDINGS BY TIME OF DIAGNOSIS IN FEMALES WITH HYPOPITUITARISM ATTRIBUTED TO LYMPHOCYTIC HYPOPHYSITIS.

OBJECTIVE To describe the various patterns of presentation, including assisting analyses, associated with the timing of diagnosis of females with hypopituitarism and suspected clinical diagnosis of lymphocytic hypophysitis. METHODS A retrospective study of 9 consecutive females with pituitary dysfunction developed during or after pregnancy. All subjects were treated in our clinics between 2008 and 2014. Data were collected on clinical characteristics, pituitary hormone levels, and imaging findings. RESULTS The study group included 9 patients with a mean age 33.7 ± 7.8 years at delivery. The probable cause of disease was lymphocytic hypophysitis. Headache or specific symptoms/signs of hypopituitarism appeared within 1 year of delivery. Five patients had headache, and 8 had difficulty breastfeeding or amenorrhea. Laboratory findings included central hypocortisolism (8/9 patients), hypogonadotropic hypogonadism (8/9), and central hypothyroidism (6/7). Insulin-like growth factor-1 (IGF-1) levels were low in 8/8 patients. Prolactin levels were low in 3/9 patients, and 1 patient had diabetes insipidus. Seven patients were diagnosed less than 1 year from symptom onset; 4 (57%) complained of headaches, and 5 (71%) had panhypopituitarism. Two patients were diagnosed later. Both had difficulty breastfeeding and amenorrhea, and one also had headaches. Both had panhypopituitarism and reduced pituitary volume. None of the patients fully recovered pituitary function. Normalization of the thyrotroph axis occurred in 3 patients, gonadotroph function in 3, the corticotroph axis in 2, and IGF-1 normalized in 1 subject. CONCLUSION Hypopituitarism attributed to lymphocytic hypophysitis may present during pregnancy or early postpartum period with a clear clinical picture, or later, with indolent and nonspecific symptoms and signs.