They recovered (helped by vomiting), but an ingestion apparently of about 10,000 mg was fatal, as was an injection. They commented that "Serious nicotine poisoning seems normally prevented by the fact that relatively low doses of nicotine cause nausea and vomiting, which stops users from further intake." Four adults died in the US and Europe, after intentionally ingesting liquid. Two children, one in the US in 2014 and another in Israel in 2013, died after ingesting liquid nicotine.The discrepancy between the historically stated 60-mg dose and published cases of nicotine intoxication has been noted previously (Matsushima et al. 1995; Metzler et al. 2005). Nonetheless, this value is still widely accepted over the 500mg figure as the basis for safety regulations of tobacco and other nicotine-containing products (such as the EU wide TPD, set at a maximum of 20mg. Pathophysiology
The symptoms of nicotine poisoning are caused by effects at nicotinic cholinergic receptors. Nicotine is an agonist at nicotinic acetylcholine receptor which are present in the central and autonomic nervous systems, and the neuromuscular junction. At low doses nicotine causes stimulatory effects on these receptors, however, higher doses or more sustained exposures can cause inhibitory effects leading to neuromuscular blockade.It is sometimes reported that people poisoned by organophosphate insecticides experience the same symptoms as nicotine poisoning. Organophosphates inhibit an enzyme called acetylcholinesterase, causing a buildup of acetylcholine, excessive stimulation of all types of cholinergic neurons, and a wide range of symptoms.
The same TSH concentration may have a different meaning whether it is used for diagnosis of thyroid dysfunction or for monitoring of substitution therapy with levothyroxine. Reasons for this lack of generalisation are Simpsons paradox and the fact that the TSH-T3 shunt is disrupted in treated hypothyroidism, so that the shape of the relation between free T4 and TSH concentration is distorted. Therapeutic
A synthetic drug called recombinant human TSH alpha (rhTSHα or simply rhTSH) or thyrotropin alfa (INN) is manufactured by Genzyme Corp under the trade name Thyrogen. It is used to manipulate endocrine function of thyroid-derived cells, as part of the diagnosis and treatment of thyroid cancer. History
In 1916, Bennett M. Allen and Philip E. Smith found that the pituitary contained a thyrotropic substance. References
External links

"Thyrotropin alfa". Drug Information Portal. U.S. National Library of Medicine. TSH at Lab Tests Online
MedlinePlus Encyclopedia: 003684
Thyrotropin at the US National Library of Medicine Medical Subject Headings (MeSH)