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.

A woman in her fifties with abdominal pain and severe lactic acidosis. / En kvinne i 50-årene med magesmerter og alvorlig laktacidose.

BACKGROUND: Pheochromocytoma is referred to as 'the great mimic' with a broad spectrum of presenting symptoms. In the following case, the diagnosis had an unusual presentation as a medical emergency - pheochromocytoma crisis. CASE PRESENTATION: A previously healthy woman in her fifties was admitted due to abdominal pain and dyspnoea. At admission she was haemodynamically stable, with stable respiration, but arterial blood gas showed serious lactic acidosis with pH 6.8 (7.35-7.45), HCO3 3 mmol/l (22-26) and lactate 28 mmol/L (0.4-1.8). Her haemoglobin level was 12 g/dl (11,7-17,0). Further examination with CT and gastroscopy confirmed a duodenal bleeding. The lactic acidosis was corrected quickly, but the patient developed acute kidney injury, rhabdomyolysis and increased liver enzymes. The complex composition of organ manifestations could not be explained by the duodenal bleeding alone. An adrenal mass with high density was identified through re-evaluation of the CT scans. In the following case, a duodenal bleeding provoked catecholamine-induced haemodynamic instability and end-organ damage in a patient with an undiagnosed pheochromocytoma. INTERPRETATION: Endocrine emergencies are important differential diagnoses in critically ill patients. Pheochromocytoma crisis most commonly presents as hypertensive crisis or catecholamine cardiomyopathy but can also lead to lactic acidosis and multi-organ failure.

Impact of EMG Changes in Continuous Vagal Nerve Monitoring in High-Risk Endocrine Neck Surgery.

BACKGROUND: Continuous vagal intraoperative neuromonitoring (CIONM) of the recurrent laryngeal nerve (RLN) may reduce the risk of RLN lesions during high-risk endocrine neck surgery such as operation for large goiter potentially requiring transsternal surgery, advanced thyroid cancer, and recurrence. METHODS: Fifty-five consecutive patients (41 female, median age 61 years, 87 nerves at risk) underwent high-risk endocrine neck surgery. CIONM was performed using the commercially available NIM-Response 3.0 nerve monitoring system with automatic periodic stimulation (APS) and matching endotracheal tube electrodes (Medtronic Inc.). All CIONM events (decreased amplitude/increased latency) were recorded. RESULTS: APS malfunction occurred on three sides (3%). A total of 138 CIONM events were registered on 61 sides. Of 138, 47 (34%) events were assessed as imminent (13 events) or potentially imminent (34 events) lesions, whereas 91 (66%) were classified as artifacts. Loss of signal was observed in seven patients. Actions to restore the CIONM baseline were undertaken in 58/138 (42%) events with a median 60 s required per action. Four RLN palsies (3 transient, 1 permanent) occurred: one in case of CIONM malfunction, two sudden without any significant previous CIONM event, and one without any CIONM event. The APS vagus electrode led to temporary damage to the vagus nerve in two patients. CONCLUSIONS: CIONM may prevent RLN palsies by timely recognition of imminent nerve lesions. In high-risk endocrine neck surgery, CIONM may, however, be limited in its utility by system malfunction, direct harm to the vagus nerve, and particularly, inability to indicate RLN lesions ahead in time.