Objective: It is unclear whether mortality still is increased in acromegaly and whether there are gender-related differences. We dynamically assessed outcome during long-term follow-up in our nationwide cohort. Patients and methods: We studied standardized mortality ratios (SMRs) relative to the general population and causes of death in acromegaly (n=333) compared with age- and gender-matched controls (n=4995). Results: During 20 (0–33) years follow-up, 113 (34%) patients (n=333, 52% women) and 1334 (27%) controls (n=4995) died (P=0.004). SMR (1.9, 95% CI: 1.53–2.34, P<0.001) and all-cause mortality (OR 1.6, 95% CI: 1.2–2.2, P<0.001) were increased in acromegaly. Overall distribution of causes of death (P<0.001) differed between patients and controls but not cardiovascular (34% vs 33%) or cancer deaths (27% vs 27%). In acromegaly, but not in controls, causes of deaths shifted from 44% cardiovascular and 28% cancer deaths during the first decade, to 23% cardiovascular and 35% cancer deaths during the next two decades. In acromegaly, cancer deaths were mostly attributed to pancreatic adenocarcinoma (n=5), breast (n=4), lung (n=3) and colon (n=3) carcinoma. In acromegaly, men were younger than women at diagnosis (median 44.5 vs 50 years, P<0.001) and death (67 vs 76 years, P=0.0015). Compared with controls, women (36% vs 25%, P<0.01), but not men (31% vs 28%, P=0.44), had increased mortality. Conclusions: In acromegaly, men are younger at diagnosis and death than women. Compared with controls, mortality is increased during 20 years of follow-up, especially in women. Causes of deaths shift from predominantly cardiovascular to cancer deaths.

Background: Parathyroid carcinoma (PC) is rare and diagnostically challenging. Reported outcomes are rather poor and the incidence might be increasing. Material and methods: We performed a nationwide study on all cases (n= 32) diagnosed in 2000–2011 in Finland, and compared clinical and histopathological characteristics and outcome to atypical parathyroid (APA; n= 28) and parathyroid adenomas (PA; n= 72). The incidence in years 1955–1999 was compared to that in 2000–2013. Results: Preoperatively, calcium and parathyroid hormone concentrations were higher in PC compared to APA and PA (1.76, 1.56 and 1.44 mmol/l, p < .001; and 989, 355 and 160 μmol/l, p < .001, respectively). Calcium was ≤1.77 mmol/l for all PAs. Hospitalization (44% vs. 22% and 3%, respectively, p = .01), renal (50% vs. 48% vs. 22%, respectively, p = .01) and bone (47% vs. 15% vs. 38%, respectively p = .002) manifestations were more common. PC and APA tumors were larger than PA (p < .001). Histopathological characteristics of PC compared to PA are increased mitotic activity (p= .001), chief cells (p = .003), diffuse growth pattern (p < .001), higher Ki67 (p< .001) and negative parafibromin (p < .001). One PC (1/18) and one APA (1/16) patient had a CDC73 mutation. After 6.7 (2–13.9) years of follow-up, 9.4% of PC had residual, 21% recurrent disease and 12.5% died of disease. Overall mortality did not differ between subgroups (p = .094). Recurrent PC was characterized by vascular invasion, lymph node metastases, high mitotic activity, necrosis and negative parafibromin. Incidence increased from 1.42 (range 0.52–2.14) to 7.14 (range 3.42–10.38)/10.000.000/years; (p < .001). Conclusions: PC associates with severe primary hyperparathyroidism and must be suspected if calcium ≥1.77 mmol/l. The prevalence of CDC73 germline mutations in PC and APA in Finland is 6%. PC has distinct histopathological characteristics and its incidence has increased over the past decades.

Introduction: Adult hypophosphatasia (HPP) is characterized by low serum alkaline phosphatase (S-ALP) and poorly healing fractures due to ALPL gene mutations. Increased S-ALP and fracture repair were reported in two patients treated with teriparatide, PTH 1-34. The effects of full-length PTH 1-84 have not been studied. Methods: Two 56- and 64-yr-old sisters (patients 1 and 2) with HPP and with long-standing, painful femur fractures received PTH 1-84 (Preotact, 100 μg/d sc) for 7 and 18 months, respectively. Patient 1 had another treatment 8 months later because of new femur fractures. We characterized the underlying mutation(s) and treatment effects according to S-ALP, bone markers, serum ionized calcium, plasma phosphate (P-Pi), pain, mobility, and fracture healing. Results: Both patients were compound heterozygotes for a p.G339R and p.E191K ALPL mutation. S-ALP increased significantly, 4.9- and 6.8-fold in patient 1 and 2.7-fold in patient 2. Responses decreased at 6 months but remained higher than basal activity. Serum N-terminal propeptide of type I procollagen and urinary N-telopeptide of type I collagen increased 14- to 19-fold and 9–5-fold in patient 1, respectively, and 9- and 3-fold in patient 2. P-Pi fluctuated in patient 1 and increased in patient 2. Pain and mobility improved promptly. Fractures healed after 7–8 months of treatment in patient 1 and at 15 months in patient 2. Conclusion: PTH 1-84 improves pain, mobility, and fracture repair in adult HPP, even after repeat treatment. Residual activity of the p.E191K ALPL gene mutation could explain why PTH can stimulate S-ALP. P-Pi concentrations may modulate the response.

All patients with primary hyperparathyroidism should undergo localization studies before reoperation, but it is not known which method is most accurate. The purpose of this prospective study was to compare the performance of planar scintigraphy with ¹²³I/^99mTc-sestamibi, ^99mTc-sestamibi SPECT (SPECT/CT), ¹¹C-methionine PET/CT, and selective venous sampling (SVS) in persistent primary hyperparathyroidism. Methods: Twenty-one patients referred for reoperation of persistent hyperparathyroidism were included and investigated with ¹²³I/^99mTc-sestamibi, SPECT/CT (n = 19), ¹¹C-methionine PET/CT, and SVS (n = 18) before reoperation. All patients had been operated on 1–2 times previously because of hyperparathyroidism. The results of the localization studies were compared with operative findings, histology, and biochemical cure. Results: Eighteen (86%) of 21 patients were biochemically cured. Nineteen parathyroid glands (9 adenomas, 1 atypical adenoma, and 9 hyperplastic glands) were removed from 17 patients, and 1 patient who was biochemically cured had an unclear histology result. The accuracy for localizing a pathologic parathyroid gland to the correct side of the neck was 59% (95% confidence interval [CI], 36%–79%) for ¹²³I/^99mTc-sestamibi, 19% (95% CI, 5%–42%) for SPECT/CT, 65% (95% CI, 43%–84%) for ¹¹C-methionine PET/CT, and 40% (95% CI, 19%–65%) for SVS (P < 0.01 for ¹²³I/^99mTc-sestamibi vs. SPECT/CT). The corresponding accuracy for the correct quadrant or more specific site was 48% (95% CI, 27%–69%) for ¹²³I/^99mTc-sestamibi, 14% (95% CI, 3%–36%) for SPECT/CT, 61% (95% CI, 39%–80%) for ¹¹C-methionine PET/CT, and 25% (95% CI, 9%–49%) for SVS (P < 0.02 for ¹²³I/^99mTc-sestamibi vs. SPECT/CT). In the 3 patients not cured, preoperative ¹²³I/^99mTc-sestamibi and SPECT/CT remained negative, SVS was false predictive in all, and ¹¹C-methionine PET/CT in 1. ¹¹C-methionine PET/CT accurately revealed the pathologic gland in 4 of 8 (50%) patients with a negative ¹²³I/^99mTc-sestamibi scan result, all of whom were biochemically cured after reoperation. Conclusion: Planar scintigraphy with ¹²³I/^99mTc-sestamibi performs well in complicated primary hyperparathyroidism and is recommended as first-line imaging before reoperation. ¹¹C-methionine PET/CT provides valuable additional information if ¹²³I/^99mTc-sestamibi scan results remain negative. ^99mTc-sestamibi SPECT/CT and SVS provide no additional information, compared with the combined results of ¹²³I/^99mTc-sestamibi and ¹¹C-methionine PET/CT imaging.

Adrenocortical carcinoma (ACC) is a rare endocrine carcinoma with poor 5-year survival rates of < 40%. According to the literature, ACC is rarely an incidental imaging finding. However, presentation, treatment and outcome may differ in modern series.