Making wise decisions for completion thyroidectomies

Unilateral differentiated thyroid cancer (DTC) <4 cm can be treated with thyroid lobectomy or total thyroidectomy (TT), depending on the presence of high-risk features. Information about some of these features, such as micrometastasis in lymph nodes or microscopic extrathyroidal extension (ETE), are usually incidental findings that only become available after histological assessment from the first surgery. If such features or risk factors are present, physicians face the dilemma of suggesting completion thyroidectomy or not. There is often considerable room for clinical judgement in these cases, even though thyroid cancer guidelines generally say that completion thyroidectomy should be offered as if the information were available before the initial surgery. In this issue of Gland Surgery, Choi and coworkers (1) provide data that may help clinicians making their wise decisions when faced with this situation. The authors looked at patients whose American Thyroid Association (ATA) risk classification was upstaged from low to intermediate after incidental findings of lymph node micrometastasis or microscopic ETE. The authors present data from 2,830 patients treated for assumed low risk DTC with lobectomy and prophylactic ipsilateral central compartment neck dissection (CCND). Patients with lymph node metastasis >2 mm or gross ETE of the cancer were treated with TT and not included in the study. Thus, patient selection included only “the better part” of intermediate risk patients. The presence of micrometastasis or microscopic ETE, two features that according to ATA guidelines (2) would add to the argument for completion thyroidectomy, did not change the treatment strategy at the author’s clinic. This allowed the unique opportunity for the authors to compare long-term oncological outcomes for patients with micrometastasis in the central lymph nodes or microscopic ETE, to those who had not, without further surgical or radioiodine treatment

Severe hypercalcemia caused by parathyroid hormone in a rectal cancer metastasis: a case report

Background - Hypercalcemia of malignancy is relatively common in several cancers. However, in colorectal cancer, paraneoplastic phenomena that cause hypercalcemia is uncommon. In the few cases that are reported, secretion of parathyroid hormone-related peptide mediates the effect. We describe the first case of severe hypercalcemia mediated by intact parathyroid hormone secretion from a bone metastasis of colorectal origin. This was a diagnostic and therapeutic challenge. Case presentation - A 68-year-old male treated for rectal adenocarcinoma 10 years earlier developed a bone metastasis. After initial treatment of the metastasis with surgery and irradiation, he developed a relapse with severe hypercalcemia and corresponding elevated parathyroid hormone levels. The workup showed no signs of parathyroid adenomas, but the metastasis produced intact parathyroid hormone. The hypercalcemia was successfully treated by irradiation and osteoclast inhibitor, and the patient received chemotherapy. Survival was 24 months from the onset of hypercalcemia. Conclusions - Proper diagnosis of the uncommon endocrine disturbance allowed targeted therapy and avoidance of neck exploration for wrongly suspecting primary hyperparathyroidism. Intact parathyroid hormone should be measured in cases of malignant hypercalcemia

Patient-tailored levothyroxine dosage with pharmacokinetic/pharmacodynamic modeling: A novel approach after total thyroidectomy

Background: After seven decades of levothyroxine (LT4) replacement therapy, dosage adjustment still takes several months. We have developed a decision aid tool (DAT) that models LT4 pharmacometrics and enables patient-tailored dosage. The aim of this was to speed up dosage adjustments for patients after total thyroidectomy. Methods: The DAT computer program was developed with a group of 46 patients post-thyroidectomy, and it was then applied in a prospective randomized multicenter validation trial in 145 unselected patients admitted for total thyroidectomy for goiter, differentiated thyroid cancer, or thyrotoxicosis. The LT4 dosage was adjusted after only two weeks, with or without application of the DAT, which calculated individual free thyroxine (fT4) targets based on four repeated measurements of fT4 and thyrotropin (TSH) levels. The individual TSH target was either <0.1, 0.1–0.5, or 0.5–2.0 mIU/L, depending on the diagnosis. Initial postoperative LT4 dosage was determined according to clinical routine without using algorithms. A simplified DAT with a population-based fT4 target was used for thyrotoxic patients who often went into surgery after prolonged TSH suppression. Subsequent LT4 adjustments were carried out every six weeks until target TSH was achieved. Results: When clinicians were guided by the DAT, 40% of patients with goiter and 59% of patients with cancer satisfied the narrow TSH targets eight weeks after surgery, as compared with only 0% and 19% of the controls, respectively. The TSH was within the normal range in 80% of DAT/goiter patients eight weeks after surgery as compared with 19% of controls. The DAT shortened the average dosage adjustment period by 58 days in the goiter group and 40 days in the cancer group. For thyrotoxic patients, application of the simplified DAT did not improve the dosage adjustment. Conclusions: Application of the DAT in combination with early postoperative TSH and fT4 monitoring offers a fast approach to LT4 dosage after total thyroidectomy for patients with goiter or differentiated thyroid cancer. Estimation of individual TSH-fT4 dynamics was crucial for the model to work, as removal of this feature in the applied model for thyrotoxic patients also removed the benefit of the DAT

Hippocampal growth hormone modulates relational memory and the dendritic spine density in CA1

Growth hormone (GH) deficiency is associated with cognitive decline which occur both in normal aging and in endocrine disorders. Several brain areas express receptors for GH although their functional role is unclear. To determine how GH affects the capacity for learning and memory by specific actions in one of the key areas, the hippocampus, we injected recombinant adeno-associated viruses (rAAVs) in male rats to express green fluorescent protein (GFP) combined with either GH, antagonizing GH (aGH), or no hormone, in the dorsal CA1. We found that aGH disrupted memory in the Morris water maze task, and that aGH treated animals needed more training to relearn a novel goal location. In a one-trial spontaneous location recognition test, the GH treated rats had better memory performance for object locations than the two other groups. Histological examinations revealed that GH increased the dendritic spine density on apical dendrites of CA1, while aGH reduced the spine density. GH increased the relative amount of immature spines, while aGH decreased the same amount. Our results imply that GH is a neuromodulator with strong influence over hippocampal plasticity and relational memory by mechanisms involving modulation of dendritic spines. The findings are significant to the increasing aging population and GH deficiency patients

Prediction of thyroid nodule histopathology by expert ultrasound evaluation

Objective - The basis of thyroid nodule diagnostics is ultrasound-guided fine needle biopsy with cytological evaluation (FNC) if ultrasound appearance is not clearly benign. The aim of this study was to investigate the predictive potential of dedicated, expert high-resolution ultrasound, to see if histopathological entities of thyroid nodules can be diagnosed without invasive FNC biopsies. Design - Prospective case-cohort study. Methods - 187 patients with 221 thyroid nodules were examined with ultrasound and prospectively assigned to the expected histopathological diagnosis: colloid nodule, adenomatoid colloid nodule, follicular adenoma, follicular carcinoma, follicular variant of papillary thyroid carcinoma, papillary thyroid carcinoma, or other thyroid cancer. In 101 of these, we later obtained histopathological reports for comparison. Results - Overall accuracy for classification into discrete histopathological categories by expert ultrasound was 71.3% and Cohen’s Kappa was 0.62. The sensitivity and specificity for detecting malignancy were 97.3% and 78.1%. The diagnostic accuracy for malignancy was 85.1%. ACR-TIRADS scores for the same nodules had a sensitivity of 97.3%, specificity of 26.6%, and accuracy of 52.5%. Conclusion - Dedicated expert high-resolution ultrasound without FNC can reliably distinguish benign vs malignant nodules, but also differentiate between several histopathological entities in thyroid nodules. There is potential for a reduction in the number of invasive FNC biopsies and diagnostic operations

Supporting online material is available on Science Online

To determine how spatial scale is represented in the pyramidal cell population of the hippocampus, we recorded neural activity at multiple longitudinal levels of this brain area while rats ran back and forth on an 18-meter-long linear track. CA3 cells had well-defined place fields at all levels. The scale of representation increased almost linearly from &lt;1 meter at the dorsal pole to~10 meters at the ventral pole. The results suggest that the place-cell map includes the entire hippocampus and that environments are represented in the hippocampus at a topographically graded but finite continuum of scales. A lthough the basic intrinsic circuitry of the hippocampus is similar along the entire dorsoventral axis of the structure (1), dorsal and ventral regions may not have similar functions. Dorsal and intermediate regions are preferentially connected, via the dorsolateral and intermediate bands of the entorhinal cortex, to visual and somatosensory cortices important for accurate spatial navigation (2-5), and selective lesions in these hippocampal regions can lead to impairments in spatial learning Conventional recording environments may be too small to visualize the most extended hippocampal representations (figs. S2 to S4 and supporting online text). Thus, we tested the animals on an 18-m-long linear track. Well-delineated place fields, defined as spatially stable contiguous regions with firing above 20% of the peak rate, could be found at all longitudinal levels of the hippocampu